The Experts below are selected from a list of 253389 Experts worldwide ranked by ideXlab platform
Subrata Haldar - One of the best experts on this subject based on the ideXlab platform.
-
abstract 139 microrna 375 and microrna 221 potential noncoding rnas associated with antiproliferative activity of benzyl isothiocyanate in pancreatic cancer
Cancer Research, 2011Co-Authors: Aruna Basu, Carlo M Croce, Hansjuerg Alder, Amer Khiyami, Patrick Leahy, Subrata HaldarAbstract:The deregulated presence or absence of microRNAs (miRNAs) might play an important role in molecular pathways leading to neoplastic transformation. At present, it is also thought that the approaches to interfere miRNA functions should be helpful for developing novel therapeutic opportunities for human cancer. In this study, we provide evidence that the anticancer agent benzyl isothiocyanate (BITC) has the ability to modulate the level of miRNAs such as miR-221 and Mir-375, known to be abnormally expressed in pancreatic cancer patients. Interestingly, ectopic expression of Mir-375 or the enforced silencing of miR-221 in cultured pancreatic cancer cells attenuates cell viability and sensitizes antiproliferative action of BITC. We also show that the expression of putative tumor suppressor Mir-375 is more abundant in nonpathological mice pancreata than those with Kras G12D -driven pancreatic intraepithelial neoplasia (PanIN). To the contrary, the expression of oncogenic miR-221 is significantly elevated in the mouse pancreas with PanIN lesions. Although Mir-375 has been shown to be aberrantly expressed in pancreatic cancer patients, there has not been a comprehensive study to investigate the molecular pathways targeted by this miRNA in pancreatic cancer cells. Further analysis by gene expression microarray revealed that IGFBP5 and CAV-1, potential biomarkers of pancreatic cancer, were significantly downregulated in cells transfected with Mir-375. Correlatively, elevated expression of IGFBP5 and CAV-1 was evident in the mouse pancreas with preneoplastic lesions in which the expression of Mir-375 wanes. Taken together, our findings suggest that anticancer agent BITC might target the expression of miR-221 and Mir-375 to switch hyperproliferative pancreatic cancer cells to a hypoproliferative state.
-
microrna 375 and microrna 221 potential noncoding rnas associated with antiproliferative activity of benzyl isothiocyanate in pancreatic cancer
Genes & Cancer, 2011Co-Authors: Aruna Basu, Carlo M Croce, Hansjuerg Alder, Amer Khiyami, Patrick Leahy, Subrata HaldarAbstract:The deregulated presence or absence of microRNAs (miRNAs) might play an important role in molecular pathways leading to neoplastic transformation. At present, it is also thought that the approaches to interfere miRNA functions should be helpful for developing novel therapeutic opportunities for human cancer. In this study, we provide evidence that the anticancer agent benzyl isothiocyanate (BITC) has the ability to modulate the level of miRNAs such as miR-221 and Mir-375, known to be abnormally expressed in pancreatic cancer patients. Interestingly, ectopic expression of Mir-375 or the enforced silencing of miR-221 in cultured pancreatic cancer cells attenuates cell viability and sensitizes antiproliferative action of BITC. We also show that the expression of putative tumor suppressor Mir-375 is more abundant in nonpathological mice pancreata than those with KrasG12D-driven pancreatic intraepithelial neoplasia (PanIN). To the contrary, the expression of oncogenic miR-221 is significantly elevated in the mouse pancreas with PanIN lesions. Although Mir-375 has been shown to be aberrantly expressed in pancreatic cancer patients, there has not been a comprehensive study to investigate the molecular pathways targeted by this miRNA in pancreatic cancer cells. Further analysis by gene expression microarray revealed that IGFBP5 and CAV-1, potential biomarkers of pancreatic cancer, were significantly downregulated in cells transfected with Mir-375. Correlatively, elevated expression of IGFBP5 and CAV-1 was evident in the mouse pancreas with preneoplastic lesions in which the expression of Mir-375 wanes. Taken together, our findings suggest that anticancer agent BITC might target the expression of miR-221 and Mir-375 to switch hyperproliferative pancreatic cancer cells to a hypoproliferative state.
Feng Wu - One of the best experts on this subject based on the ideXlab platform.
-
mir 375 is involved in hippo pathway by targeting yap1 tead4 ctgf axis in gastric carcinogenesis
Cell Death and Disease, 2018Co-Authors: Wei Kang, Tingting Huang, Yuhang Zhou, Jinglin Zhang, Raymond W M Lung, Joanna H M Tong, Anthony W H Chan, Bin Zhang, Chi Chun Wong, Feng WuAbstract:Mir-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how Mir-375 is involved in Hippo pathway by targeting multiple oncogenes. Mir-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by Mir-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of Mir-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and Mir-375 in primary GCs. Mir-375 was down-regulated in GC due to promoter methylation and histone deacetylation. Mir-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of Mir-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of Mir-375. The expression of three genes showed a negative correlation with Mir-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of Mir-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or Mir-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, Mir-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.
Robert J Lee - One of the best experts on this subject based on the ideXlab platform.
-
delivery of mir 375 and doxorubicin hydrochloride by lipid coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
International Journal of Nanomedicine, 2017Co-Authors: Huiying Xue, Tan Yang, Yong Liu, Weigang Yuan, Jia You, Robert J LeeAbstract:Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that Mir-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and Mir-375 (LHD/Mir-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/Mir-375 overcame drug efflux and delivered Mir-375 and DOX into MDR HepG2/ADR cells or HCC tissues. Mir-375 delivered by LHD/Mir-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of Mir-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/Mir-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that Mir-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of Mir-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application.
Wei Kang - One of the best experts on this subject based on the ideXlab platform.
-
mir 375 is involved in hippo pathway by targeting yap1 tead4 ctgf axis in gastric carcinogenesis
Cell Death and Disease, 2018Co-Authors: Wei Kang, Tingting Huang, Yuhang Zhou, Jinglin Zhang, Raymond W M Lung, Joanna H M Tong, Anthony W H Chan, Bin Zhang, Chi Chun Wong, Feng WuAbstract:Mir-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how Mir-375 is involved in Hippo pathway by targeting multiple oncogenes. Mir-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by Mir-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of Mir-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and Mir-375 in primary GCs. Mir-375 was down-regulated in GC due to promoter methylation and histone deacetylation. Mir-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of Mir-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of Mir-375. The expression of three genes showed a negative correlation with Mir-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of Mir-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or Mir-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, Mir-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.
-
Mir-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis
Nature Publishing Group, 2018Co-Authors: Wei Kang, Tingting Huang, Yuhang Zhou, Jinglin Zhang, Raymond W M Lung, Joanna H M Tong, Anthony W H Chan, Bin Zhang, Chi Chun WongAbstract:Abstract Mir-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how Mir-375 is involved in Hippo pathway by targeting multiple oncogenes. Mir-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by Mir-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of Mir-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and Mir-375 in primary GCs. Mir-375 was down-regulated in GC due to promoter methylation and histone deacetylation. Mir-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of Mir-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of Mir-375. The expression of three genes showed a negative correlation with Mir-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of Mir-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or Mir-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, Mir-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis
Tan Yang - One of the best experts on this subject based on the ideXlab platform.
-
delivery of mir 375 and doxorubicin hydrochloride by lipid coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
International Journal of Nanomedicine, 2017Co-Authors: Huiying Xue, Tan Yang, Yong Liu, Weigang Yuan, Jia You, Robert J LeeAbstract:Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that Mir-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and Mir-375 (LHD/Mir-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/Mir-375 overcame drug efflux and delivered Mir-375 and DOX into MDR HepG2/ADR cells or HCC tissues. Mir-375 delivered by LHD/Mir-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of Mir-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/Mir-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that Mir-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of Mir-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application.
-
anti tumor efficiency of lipid coated cisplatin nanoparticles co loaded with microrna 375
Theranostics, 2016Co-Authors: Tan Yang, Pengxuan Zhao, Chuanchuan He, Xingxing He, Zhao Rong, Weijie Li, Bin Li, Guangya XiangAbstract:One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/Mir-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/Mir-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the Mir-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/Mir-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the Mir-375 in lysosomes. Importantly, NPC/Mir-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/Mir-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with Mir-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.