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Fei Liu - One of the best experts on this subject based on the ideXlab platform.
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Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis
2020Co-Authors: Qiaoming Zhi, Dongming Zhu, Daiwei Wan, Ye Han, Fei Liu, Min JiangAbstract:Abstract Background The polyether antibiotic Nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of Nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of Nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of Nigericin. In addition, the inhibitory effects of Nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that Nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that Nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by Nigericin. Meanwhile, the inhibitory effects of Nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of Nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.
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Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing.
Frontiers in oncology, 2020Co-Authors: Guanzhuang Gao, Daiwei Wan, Ye Han, Fei Liu, Yuting Kuang, Chen Dai, Sentai Wang, Guobang Wei, Qiaoming ZhiAbstract:Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibit the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA. Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing. Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process. Conclusions: These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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Molecular screening for Nigericin treatment in pancreatic cancer by high-throughput RNA sequencing
2020Co-Authors: Qiaoming Zhi, Ye Han, Fei Liu, Yuting Kuang, Guanzhuang Gao, Chen Dai, Sentai Wang, Guobang Wei, Daiwei WanAbstract:Abstract Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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High-throughput sequencing of circRNAs reveals novel insights into mechanisms of Nigericin in pancreatic cancer.
BMC genomics, 2019Co-Authors: Jiaqing Shen, Daiwei Wan, Ye Han, Fei Liu, Shangbo Hua, Qian Chen, Rui Ren, Xiaobo GuoAbstract:Our previous study had proved that Nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of Nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after Nigericin exposure on pancreatic cancer (PC) cells. In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in Nigericin damage. By the bioinformatics method, our data will facilitate the understanding of Nigericin in PC cells, and provide new insight into the molecular mechanism of Nigericin toward cancer cells. This is the first report that discusses the potential functions of Nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of Nigericin-mediated anti-cancer mechanisms in PC.
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Nigericin exerts anticancer effects on human colorectal cancer cells by inhibiting wnt β catenin signaling pathway
Molecular Cancer Therapeutics, 2018Co-Authors: Fei Liu, Daiwei Wan, Ye Han, Shangbo Hua, Yilin Wang, Weichang Chen, Yuting Kuang, Jianming Shi, Qiaoming ZhiAbstract:Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of Nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that Nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that Nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that Nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of Nigericin via a β-catenin-dependent signaling mechanism, we established the stably β-catenin overexpression colorectal cancer cells. Western blot, SuperTOPFlash luciferase reporter, and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and Nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of Nigericin toward cancer cells, and suggest possible clinical application in colorectal cancer. Mol Cancer Ther; 17(5); 952-65. ©2018 AACR.
Marie E. Varnes - One of the best experts on this subject based on the ideXlab platform.
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Reduction of Intracellular pH Is Not the Mechanism for the Synergistic Interaction Between Photodynamic Therapy and Nigericin
Photochemistry and photobiology, 1996Co-Authors: Marie E. Varnes, Marian T. Bayne, Gary R. BrightAbstract:Abstract— Previous studies showed that photodynamic therapy (PDT) sensitized by aluminum phthalocyanine can be dramatically potentiated by the K+/H+ ionophore Nigericin. Nigericin equilibrates intracellular pH (pHi) and extracellular pH (pHe) and is most effective in potentiating PDT damage when cells are in an acidic environment (pH 6.5-6.7). We therefore hypothesized that the ability of Nigericin to lower pHi is causally related to its ability to potentiate PDT. To test this, the pHi of A549 cells was reduced using pHe-adjusted growth medium, with or without addition of amiloride and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, inhibitors of the membrane-based exchangers responsible for regulating pHi. Using fluorescence ratio imaging, we found that pHi can be equilibrated to within ± 0.05 pH unit, in the pH range of 6.0-6.8, for up to 1 h after pHe adjustment. Cells equilibrated to various pHi were subjected to PDT at various light fluences, then plated for clonogenic survival immediately after PDT treatment. There is no significant effect of lowering pHi, to values as low as 6.23, on the toxicity of PDT, regardless of whether pHi is lowered by adjustment of the medium alone or by addition of exchange inhibitors. However, cells equilibrated to pHi 6.0 are more sensitive to PDT, with survival reduced by 1 log at 20 kJ/m2 and 1.5 log at 30 kJ/m2, relative to cells treated at a pHi of 6.8 (controls). In contrast, 20 μM Nigericin in medium at pHe 6.7 reduces pHi to 6.55, but reduces the surviving fraction at 20 kJ/m2 by nearly 3 logs relative to controls. These data conclusively demonstrate that the ability of Nigericin to potentiate PDT is not directly related to its ability to lower pHi. Furthermore, they show that the expression of PDT damage is independent of pHi, except at the very low value of 6.0. Photodynamic therapy does not induce apoptosis in A549 cells, at surviving fractions of 0.1 to 0.01, under any of the treatment conditions used in this study.
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Elevation of GRP-78 and loss of HSP-70 following photodynamic treatment of V79 cells: sensitization by Nigericin.
Photochemistry and photobiology, 1995Co-Authors: Liang-yan Xue, Munna L. Agarwal, Marie E. VarnesAbstract:Abstract— Chinese hamster V79 cells were treated with photodynamic therapy (PDT) sensitized by aluminum phthalocyanine (AlPc) or with the ionophore Nigericin or with combinations of PDT and Nigericin. We previously showed that PDT and Nigericin interact synergistically in the killing of these cells; i.e. doses of PDT that kill no more than 10% of the cells in combination with nontoxic exposures to Nigericin lead to a loss of clonogenicity of three to five orders of magnitude. Photodynamic therapy induces an enhanced rate of expression of the stress gene grp-78 both at the transcriptional and trans-lational levels and causes a decrease in the synthesis of the constitutive heat shock protein HSP-70 as well as in expression of HSP-70 mRNA. When the cells are exposed to PDT in the presence of Nigericin, these effects are elicited at three- to four-fold lower PDT doses. Thus, PDT in the presence of Nigericin is much more effective in inducing the changes in gene expression than is PDT alone. In the absence of Nigericin the PDT dose inducing a two-fold increase in GRP-78 accumulation causes little or no loss of clonogenicity. In the presence of Nigericin, however, the PDT dose leading to a similar change in GRP-78 level produces up to a 50% loss of clonogenicity. The fact that Nigericin is dose-modifying for both cell killing and stress responses suggests that Nigericin either increases the yield of oxidative damage from a given dose of PDT or magnifies the cellular response to a constant level of oxidative stress.
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effect of the k h ionophore Nigericin on response of a549 cells to photodynamic therapy and tert butylhydroperoxide
Free Radical Biology and Medicine, 1993Co-Authors: Marie E. Varnes, Marian T. Bayne, Harry J. Menegay, Stephen W. TuttleAbstract:Abstract The K+/H+ ionophore negericin dramatically increases killing of V79 cells and A549 cells by photodynamic therapy (PDT) sensitized by chloroaluminum phthalocyanine. Previous studies suggested that the interaction between PDT and Nigericin is related to the ability of this ionophore to reduce intracellular pH (pHi). The present study was undertaken to test the possibility that Nigericin, by lowering pHi, inhibits reductive detoxification of PDT-produced peroxides by enzymes of the glutathione (GSH) redox cycle and the pentose cycle. To test this possibility we examined the effects of Nigericin on the toxicity and metabolism of a model peroxide, tert-butylhydroperoxide (tert-BOOH), in A549 cells, a cell line in which the GSH redox cycle is known to be the principal pathway for reduction and detoxification of tert-BOOH. We found that Nigericin equilibrates pHi of A549 cells with extracellular pH (pHe) in a time-dependent manner. It increases the toxicity of tert-BOOH toward A549 cells, inhibits loss of tert-BOOH from the buffer overlying the cells, and reduces the rate of 14CO2 release from radiolabelled glucose, which is measure of pentose cycle activity. These effects are significantly greater at pHe 6.40 than at 7.40. Monensin, a Na+/H+ ionophore which does not reduce pHi, does not enhance the toxicity of tert-BOOH and has only a minimal effect on tert-BOOH reduction. These data suggest that Nigericin-induced inhibition of peroxide detoxification is at least a plausible mechanism by which the ionophore might interact with PDT.
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Effect of the K+/H+ ionophore Nigericin on response of A549 cells to photodynamic therapy and tert-butylhydroperoxide.
Free radical biology & medicine, 1993Co-Authors: Marie E. Varnes, Marian T. Bayne, Harry J. Menegay, Stephen W. TuttleAbstract:Abstract The K+/H+ ionophore negericin dramatically increases killing of V79 cells and A549 cells by photodynamic therapy (PDT) sensitized by chloroaluminum phthalocyanine. Previous studies suggested that the interaction between PDT and Nigericin is related to the ability of this ionophore to reduce intracellular pH (pHi). The present study was undertaken to test the possibility that Nigericin, by lowering pHi, inhibits reductive detoxification of PDT-produced peroxides by enzymes of the glutathione (GSH) redox cycle and the pentose cycle. To test this possibility we examined the effects of Nigericin on the toxicity and metabolism of a model peroxide, tert-butylhydroperoxide (tert-BOOH), in A549 cells, a cell line in which the GSH redox cycle is known to be the principal pathway for reduction and detoxification of tert-BOOH. We found that Nigericin equilibrates pHi of A549 cells with extracellular pH (pHe) in a time-dependent manner. It increases the toxicity of tert-BOOH toward A549 cells, inhibits loss of tert-BOOH from the buffer overlying the cells, and reduces the rate of 14CO2 release from radiolabelled glucose, which is measure of pentose cycle activity. These effects are significantly greater at pHe 6.40 than at 7.40. Monensin, a Na+/H+ ionophore which does not reduce pHi, does not enhance the toxicity of tert-BOOH and has only a minimal effect on tert-BOOH reduction. These data suggest that Nigericin-induced inhibition of peroxide detoxification is at least a plausible mechanism by which the ionophore might interact with PDT.
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Inhibition of recovery from potentially lethal radiation damage in A549 cells by the K+H+ ionophore Nigericin
International journal of radiation oncology biology physics, 1991Co-Authors: Marie E. Varnes, Harry J. Menegay, David S MckennaAbstract:Abstract A549 cells held for 4 hr in Hank's balanced salt solution, after 10 Gy irradiation, exhibit potentially lethal damage recovery (PLDR) which is dependent on extracellular pH (pHe). Recovery factors of 2.2 to 3.5 are observed when pHe is 6.40 to 7.30, but recovery factors of less than 1.0 are found when pHe is reduced to 6.20 or 6.00. The K+H+ ionophore Nigericin, when added to cells post-irradiation, inhibits PLDR in a pHe-dependent manner, it is increasingly more effective as pHe is reduced from 6.80 to 6.40. The presence of Nigericin thus causes inhibition of PLDR at pHe's that normally promote recovery. The drug does not affect radiation response of A549 cells when present only during irradiation. Effects of low pHe buffer, with and without Nigericin, on intracellular pH (pHi) and on ATP levels were examined in an effort to elucidate the mechanisms for inhibition of PLDR and enhancement of radiation response. Incubation of cells in pHe 6.00 buffer results in a slight decrease in pHi and does not induce a drop in ATP levels. In contrast, post-irradiation incubation of cells in pHe 6.40 buffer containing 2 γM Nigericin causes an immediate and dramatic decrease in pHi, and a gradual loss of ATP to 30% of control levels by 4 hr. The data obtained so far suggest that a very slight lowering of pHi may influence post-irradiation holding recovery, and that the mechanisms by which pHe 6.00 buffer alone, or pHe 6.40 buffer containing Nigericin, affect holding recovery are different.
Qiaoming Zhi - One of the best experts on this subject based on the ideXlab platform.
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Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis
2020Co-Authors: Qiaoming Zhi, Dongming Zhu, Daiwei Wan, Ye Han, Fei Liu, Min JiangAbstract:Abstract Background The polyether antibiotic Nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of Nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of Nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of Nigericin. In addition, the inhibitory effects of Nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that Nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that Nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by Nigericin. Meanwhile, the inhibitory effects of Nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of Nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.
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Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing.
Frontiers in oncology, 2020Co-Authors: Guanzhuang Gao, Daiwei Wan, Ye Han, Fei Liu, Yuting Kuang, Chen Dai, Sentai Wang, Guobang Wei, Qiaoming ZhiAbstract:Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibit the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA. Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing. Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process. Conclusions: These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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Molecular screening for Nigericin treatment in pancreatic cancer by high-throughput RNA sequencing
2020Co-Authors: Qiaoming Zhi, Ye Han, Fei Liu, Yuting Kuang, Guanzhuang Gao, Chen Dai, Sentai Wang, Guobang Wei, Daiwei WanAbstract:Abstract Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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Nigericin exerts anticancer effects on human colorectal cancer cells by inhibiting wnt β catenin signaling pathway
Molecular Cancer Therapeutics, 2018Co-Authors: Fei Liu, Daiwei Wan, Ye Han, Shangbo Hua, Yilin Wang, Weichang Chen, Yuting Kuang, Jianming Shi, Qiaoming ZhiAbstract:Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of Nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that Nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that Nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that Nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of Nigericin via a β-catenin-dependent signaling mechanism, we established the stably β-catenin overexpression colorectal cancer cells. Western blot, SuperTOPFlash luciferase reporter, and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and Nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of Nigericin toward cancer cells, and suggest possible clinical application in colorectal cancer. Mol Cancer Ther; 17(5); 952-65. ©2018 AACR.
Ye Han - One of the best experts on this subject based on the ideXlab platform.
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Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis
2020Co-Authors: Qiaoming Zhi, Dongming Zhu, Daiwei Wan, Ye Han, Fei Liu, Min JiangAbstract:Abstract Background The polyether antibiotic Nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of Nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of Nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of Nigericin. In addition, the inhibitory effects of Nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that Nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that Nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by Nigericin. Meanwhile, the inhibitory effects of Nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of Nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.
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Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing.
Frontiers in oncology, 2020Co-Authors: Guanzhuang Gao, Daiwei Wan, Ye Han, Fei Liu, Yuting Kuang, Chen Dai, Sentai Wang, Guobang Wei, Qiaoming ZhiAbstract:Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibit the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA. Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing. Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process. Conclusions: These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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Molecular screening for Nigericin treatment in pancreatic cancer by high-throughput RNA sequencing
2020Co-Authors: Qiaoming Zhi, Ye Han, Fei Liu, Yuting Kuang, Guanzhuang Gao, Chen Dai, Sentai Wang, Guobang Wei, Daiwei WanAbstract:Abstract Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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High-throughput sequencing of circRNAs reveals novel insights into mechanisms of Nigericin in pancreatic cancer.
BMC genomics, 2019Co-Authors: Jiaqing Shen, Daiwei Wan, Ye Han, Fei Liu, Shangbo Hua, Qian Chen, Rui Ren, Xiaobo GuoAbstract:Our previous study had proved that Nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of Nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after Nigericin exposure on pancreatic cancer (PC) cells. In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in Nigericin damage. By the bioinformatics method, our data will facilitate the understanding of Nigericin in PC cells, and provide new insight into the molecular mechanism of Nigericin toward cancer cells. This is the first report that discusses the potential functions of Nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of Nigericin-mediated anti-cancer mechanisms in PC.
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Nigericin exerts anticancer effects on human colorectal cancer cells by inhibiting wnt β catenin signaling pathway
Molecular Cancer Therapeutics, 2018Co-Authors: Fei Liu, Daiwei Wan, Ye Han, Shangbo Hua, Yilin Wang, Weichang Chen, Yuting Kuang, Jianming Shi, Qiaoming ZhiAbstract:Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of Nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that Nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that Nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that Nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of Nigericin via a β-catenin-dependent signaling mechanism, we established the stably β-catenin overexpression colorectal cancer cells. Western blot, SuperTOPFlash luciferase reporter, and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and Nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of Nigericin toward cancer cells, and suggest possible clinical application in colorectal cancer. Mol Cancer Ther; 17(5); 952-65. ©2018 AACR.
Daiwei Wan - One of the best experts on this subject based on the ideXlab platform.
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Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis
2020Co-Authors: Qiaoming Zhi, Dongming Zhu, Daiwei Wan, Ye Han, Fei Liu, Min JiangAbstract:Abstract Background The polyether antibiotic Nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of Nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of Nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of Nigericin. In addition, the inhibitory effects of Nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that Nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that Nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by Nigericin. Meanwhile, the inhibitory effects of Nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of Nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.
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Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing.
Frontiers in oncology, 2020Co-Authors: Guanzhuang Gao, Daiwei Wan, Ye Han, Fei Liu, Yuting Kuang, Chen Dai, Sentai Wang, Guobang Wei, Qiaoming ZhiAbstract:Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibit the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA. Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing. Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process. Conclusions: These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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Molecular screening for Nigericin treatment in pancreatic cancer by high-throughput RNA sequencing
2020Co-Authors: Qiaoming Zhi, Ye Han, Fei Liu, Yuting Kuang, Guanzhuang Gao, Chen Dai, Sentai Wang, Guobang Wei, Daiwei WanAbstract:Abstract Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that Nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of Nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the Nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the Nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of Nigericin toward cancer cells, and suggested a possible clinical application in PC.
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High-throughput sequencing of circRNAs reveals novel insights into mechanisms of Nigericin in pancreatic cancer.
BMC genomics, 2019Co-Authors: Jiaqing Shen, Daiwei Wan, Ye Han, Fei Liu, Shangbo Hua, Qian Chen, Rui Ren, Xiaobo GuoAbstract:Our previous study had proved that Nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of Nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after Nigericin exposure on pancreatic cancer (PC) cells. In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in Nigericin damage. By the bioinformatics method, our data will facilitate the understanding of Nigericin in PC cells, and provide new insight into the molecular mechanism of Nigericin toward cancer cells. This is the first report that discusses the potential functions of Nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of Nigericin-mediated anti-cancer mechanisms in PC.
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Nigericin exerts anticancer effects on human colorectal cancer cells by inhibiting wnt β catenin signaling pathway
Molecular Cancer Therapeutics, 2018Co-Authors: Fei Liu, Daiwei Wan, Ye Han, Shangbo Hua, Yilin Wang, Weichang Chen, Yuting Kuang, Jianming Shi, Qiaoming ZhiAbstract:Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of Nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that Nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that Nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that Nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of Nigericin via a β-catenin-dependent signaling mechanism, we established the stably β-catenin overexpression colorectal cancer cells. Western blot, SuperTOPFlash luciferase reporter, and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and Nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of Nigericin toward cancer cells, and suggest possible clinical application in colorectal cancer. Mol Cancer Ther; 17(5); 952-65. ©2018 AACR.