The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Yasuyuki Fujiwara - One of the best experts on this subject based on the ideXlab platform.
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possible mechanism of heme oxygenase 1 expression in rat Malignant Meningioma kmy j cells subjected to talaporfin sodium mediated photodynamic therapy
Photodiagnosis and Photodynamic Therapy, 2020Co-Authors: Tsutomu Takahashi, Jiro Akimoto, Saki Suzuki, Suzuka Misawa, Yo Shinoda, Nanako Saeki, Yayoi Tsuneoka, Yasuyuki FujiwaraAbstract:Abstract Background We previously demonstrated that heme oxygenase-1 (HO-1) induction may contribute to a protective response against photodynamic therapy (PDT) using talaporfin sodium (TS) in rat Malignant Meningioma KMY-J cells. In the present study, we examined the mechanism of HO-1 induction by PDT with TS (TS-PDT) in KMY-J cells. Methods KMY-J cells were incubated with 25 μM TS for 2 h and then exposed to 664 nm diode laser irradiation at 1 J/cm2. The gene and protein expression levels of HO-1 and hypoxia-inducible factor-1α (HIF-1α) were determined by real-time RT-PCR and western blot analysis, respectively. Cell viability was measured using the cell counting kit-8 assay. Results mRNA and protein levels of HO-1 in KMY-J cells were increased significantly at 3, 6, and 9 h after laser irradiation and the increased mRNA level of HO-1 was decreased by antioxidant N-acetyl cysteine treatment. The protein level of HIF-1α, which mediates transcriptional activation of the HO-1 gene, was increased significantly at 1 h after laser irradiation. Additionally, induction of mRNA expression of HO-1 by TS-PDT was diminished by HIF-1α inhibitor echinomycin. We also demonstrated that echinomycin significantly augmented the cytotoxic effect of TS-PDT. Conclusions Our findings indicate that TS-PDT may induce HO-1 expression via reactive oxygen species production and then HIF-1 pathway activation in KMY-J cells, and the HO-1 induction may cause attenuation of the therapeutic effect of TS-PDT.
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photodynamic therapy with talaporfin sodium induces dose and time dependent apoptotic cell death in Malignant Meningioma hkbmm cells
Photodiagnosis and Photodynamic Therapy, 2019Co-Authors: Megumi Ichikawa, Jiro Akimoto, Yuichi Miki, Jun Maeda, Tsutomu Takahashi, Yasuyuki Fujiwara, Michihiro KohnoAbstract:Abstract Objective To investigate the effect of photodynamic therapy (PDT) with the talaporfin sodium (mono-L-asparthyl chlorine e6: NPe-6) on human Malignant Meningioma cell line HKBMM cells in vitro. Material and methods After incubation with NPe6 for 4 h, cells underwent PDT (diode laser irradiation: 3.4 mW/cm2 and 1 J/cm2. Cell viability was determined in 2 Malignant Meningioma cell lines (human origin; HKBMM cells and rat origin; KMY-J cells) and human Malignant glioma U251 cells with Cell Counting Kit-8 assay. The HKBMM cells were examined for caspase-3 activity, annexin V or propidium iodide (PI) staining, and lactate dehydrogenase leakage. Morphological change was also investigated with phase-contrast microscopy. Results In human Malignant Meningioma HKBMM cells, viability showed a dose- and time-dependent decrease. After 24 h of laser irradiation, NPe6 at 20 μg/ml or more induced a significant decrease in cell viability in both HKBMM cells and KMY-J cells, although they more resistance than the Malignant glioma cell line U251 cells. Two kinds of morphological change were also observed in the HKBMM cells, shrinkage of the cell body, indicating apoptosis, and swelling of the cell body, indicating necrosis. In addition, both caspase-3 activity and DNA fragmentation, biochemical markers indicative of apoptosis, showed a dose-dependent increase. The percentage of necrotic cells showing positive staining for annexin V or PI was greater than that of apoptotic cells at a high concentration of NPe6. Lactate dehydrogenase leakage, a biochemical marker of necrosis, also showed a marked increase at a high concentration of NPe6. Conclusion Photodynamic therapy with NPe6 induced dose- and time-dependent apoptosis in human Malignant Meningioma HKBMM cells. At a high concentration of NPe6, however, it induced necrosis.
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photodynamic therapy using talaporfin sodium induces heme oxygenase 1 expression in rat Malignant Meningioma kmy j cells
Journal of Toxicological Sciences, 2018Co-Authors: Tsutomu Takahashi, Jiro Akimoto, Saki Suzuki, Suzuka Misawa, Yo Shinoda, Yasuyuki FujiwaraAbstract:Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of Malignant glioma. We previously demonstrated that PDT using TS (TS-PDT) treatment exhibits anti-tumor activity against not only glioblastoma cells but also Malignant Meningioma cells. In general, various stress response proteins have been reported to affect the sensitivity determination for anticancer agents against tumor cells. However, the relationship between the therapeutic effect of TS-PDT and stress response systems in tumor cells is not adequately investigated. In this study, we investigated the gene expression of stress response proteins, including Sod1, Cat1, Gstp1, Gpx1, Nqo1, and Hmox1, in rat Malignant Meningioma KMY-J cells after treatment of TS-PDT. TS-PDT treatment significantly decreased the cell viability when compared with the no laser irradiation group. In morphological observation, TS at 25.6 µM treatment exhibited a significant cytotoxic effect after 12 hr of laser irradiation to KMY-J cells. After 3 and 6 hr of TS-PDT treatment, mRNA expression of heme oxygenase-1 (HO-1, encoded by Hmox1) was significantly increased by TS-PDT treatment. We also demonstrated that zinc protoporphyrin IX (ZnPPIX), a HO-1 inhibitor, significantly augmented the cytotoxic effect of TS-PDT treatment. These data suggest that HO-1 induction may contribute to a protective response against TS-PDT treatment in the Malignant Meningioma cells and may attenuate the therapeutic effect for TS-PDT treatment.
Lai-rong Song - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells.
Frontiers in oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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microrna 221 222 inhibits the radiation induced invasiveness and promotes the radiosensitivity of Malignant Meningioma cells
Frontiers in Oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang Jia, Guijun JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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microrna 195 functions as a tumor suppressor by directly targeting fatty acid synthase in Malignant Meningioma
World Neurosurgery, 2020Co-Authors: Lai-rong Song, Liang Wang, Jiancong Weng, Junting ZhangAbstract:Objective Meningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of Malignant Meningioma to provide more treatment strategies. Methods RNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and Malignant Meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay. Results We found fatty acid synthase (FASN) was significantly upregulated in Malignant Meningioma compared with benign Meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in Meningioma. Conclusions Our results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of Malignant Meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.
Wang Jia - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells.
Frontiers in oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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microrna 221 222 inhibits the radiation induced invasiveness and promotes the radiosensitivity of Malignant Meningioma cells
Frontiers in Oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang Jia, Guijun JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
Tsutomu Takahashi - One of the best experts on this subject based on the ideXlab platform.
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possible mechanism of heme oxygenase 1 expression in rat Malignant Meningioma kmy j cells subjected to talaporfin sodium mediated photodynamic therapy
Photodiagnosis and Photodynamic Therapy, 2020Co-Authors: Tsutomu Takahashi, Jiro Akimoto, Saki Suzuki, Suzuka Misawa, Yo Shinoda, Nanako Saeki, Yayoi Tsuneoka, Yasuyuki FujiwaraAbstract:Abstract Background We previously demonstrated that heme oxygenase-1 (HO-1) induction may contribute to a protective response against photodynamic therapy (PDT) using talaporfin sodium (TS) in rat Malignant Meningioma KMY-J cells. In the present study, we examined the mechanism of HO-1 induction by PDT with TS (TS-PDT) in KMY-J cells. Methods KMY-J cells were incubated with 25 μM TS for 2 h and then exposed to 664 nm diode laser irradiation at 1 J/cm2. The gene and protein expression levels of HO-1 and hypoxia-inducible factor-1α (HIF-1α) were determined by real-time RT-PCR and western blot analysis, respectively. Cell viability was measured using the cell counting kit-8 assay. Results mRNA and protein levels of HO-1 in KMY-J cells were increased significantly at 3, 6, and 9 h after laser irradiation and the increased mRNA level of HO-1 was decreased by antioxidant N-acetyl cysteine treatment. The protein level of HIF-1α, which mediates transcriptional activation of the HO-1 gene, was increased significantly at 1 h after laser irradiation. Additionally, induction of mRNA expression of HO-1 by TS-PDT was diminished by HIF-1α inhibitor echinomycin. We also demonstrated that echinomycin significantly augmented the cytotoxic effect of TS-PDT. Conclusions Our findings indicate that TS-PDT may induce HO-1 expression via reactive oxygen species production and then HIF-1 pathway activation in KMY-J cells, and the HO-1 induction may cause attenuation of the therapeutic effect of TS-PDT.
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photodynamic therapy with talaporfin sodium induces dose and time dependent apoptotic cell death in Malignant Meningioma hkbmm cells
Photodiagnosis and Photodynamic Therapy, 2019Co-Authors: Megumi Ichikawa, Jiro Akimoto, Yuichi Miki, Jun Maeda, Tsutomu Takahashi, Yasuyuki Fujiwara, Michihiro KohnoAbstract:Abstract Objective To investigate the effect of photodynamic therapy (PDT) with the talaporfin sodium (mono-L-asparthyl chlorine e6: NPe-6) on human Malignant Meningioma cell line HKBMM cells in vitro. Material and methods After incubation with NPe6 for 4 h, cells underwent PDT (diode laser irradiation: 3.4 mW/cm2 and 1 J/cm2. Cell viability was determined in 2 Malignant Meningioma cell lines (human origin; HKBMM cells and rat origin; KMY-J cells) and human Malignant glioma U251 cells with Cell Counting Kit-8 assay. The HKBMM cells were examined for caspase-3 activity, annexin V or propidium iodide (PI) staining, and lactate dehydrogenase leakage. Morphological change was also investigated with phase-contrast microscopy. Results In human Malignant Meningioma HKBMM cells, viability showed a dose- and time-dependent decrease. After 24 h of laser irradiation, NPe6 at 20 μg/ml or more induced a significant decrease in cell viability in both HKBMM cells and KMY-J cells, although they more resistance than the Malignant glioma cell line U251 cells. Two kinds of morphological change were also observed in the HKBMM cells, shrinkage of the cell body, indicating apoptosis, and swelling of the cell body, indicating necrosis. In addition, both caspase-3 activity and DNA fragmentation, biochemical markers indicative of apoptosis, showed a dose-dependent increase. The percentage of necrotic cells showing positive staining for annexin V or PI was greater than that of apoptotic cells at a high concentration of NPe6. Lactate dehydrogenase leakage, a biochemical marker of necrosis, also showed a marked increase at a high concentration of NPe6. Conclusion Photodynamic therapy with NPe6 induced dose- and time-dependent apoptosis in human Malignant Meningioma HKBMM cells. At a high concentration of NPe6, however, it induced necrosis.
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photodynamic therapy using talaporfin sodium induces heme oxygenase 1 expression in rat Malignant Meningioma kmy j cells
Journal of Toxicological Sciences, 2018Co-Authors: Tsutomu Takahashi, Jiro Akimoto, Saki Suzuki, Suzuka Misawa, Yo Shinoda, Yasuyuki FujiwaraAbstract:Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of Malignant glioma. We previously demonstrated that PDT using TS (TS-PDT) treatment exhibits anti-tumor activity against not only glioblastoma cells but also Malignant Meningioma cells. In general, various stress response proteins have been reported to affect the sensitivity determination for anticancer agents against tumor cells. However, the relationship between the therapeutic effect of TS-PDT and stress response systems in tumor cells is not adequately investigated. In this study, we investigated the gene expression of stress response proteins, including Sod1, Cat1, Gstp1, Gpx1, Nqo1, and Hmox1, in rat Malignant Meningioma KMY-J cells after treatment of TS-PDT. TS-PDT treatment significantly decreased the cell viability when compared with the no laser irradiation group. In morphological observation, TS at 25.6 µM treatment exhibited a significant cytotoxic effect after 12 hr of laser irradiation to KMY-J cells. After 3 and 6 hr of TS-PDT treatment, mRNA expression of heme oxygenase-1 (HO-1, encoded by Hmox1) was significantly increased by TS-PDT treatment. We also demonstrated that zinc protoporphyrin IX (ZnPPIX), a HO-1 inhibitor, significantly augmented the cytotoxic effect of TS-PDT treatment. These data suggest that HO-1 induction may contribute to a protective response against TS-PDT treatment in the Malignant Meningioma cells and may attenuate the therapeutic effect for TS-PDT treatment.
Liang Wang - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells.
Frontiers in oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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microrna 221 222 inhibits the radiation induced invasiveness and promotes the radiosensitivity of Malignant Meningioma cells
Frontiers in Oncology, 2020Co-Authors: Qing Zhang, Lai-rong Song, Xu-lei Huo, Liang Wang, Guobin Zhang, Shuyu Hao, Hai-wei Jia, Chui-lin Kong, Wang Jia, Guijun JiaAbstract:The controversy of adjuvant radiotherapy of Meningiomas is at least partially due to the insufficient understanding on Meningioma cells’ response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in Meningiomas has yet to be confirmed. Therefore, the Malignant Meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 Gy and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee’s radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for Malignant Meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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microrna 195 functions as a tumor suppressor by directly targeting fatty acid synthase in Malignant Meningioma
World Neurosurgery, 2020Co-Authors: Lai-rong Song, Liang Wang, Jiancong Weng, Junting ZhangAbstract:Objective Meningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of Malignant Meningioma to provide more treatment strategies. Methods RNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and Malignant Meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay. Results We found fatty acid synthase (FASN) was significantly upregulated in Malignant Meningioma compared with benign Meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in Meningioma. Conclusions Our results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of Malignant Meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.