期刊
ONCOTARGETS AND THERAPY
卷 12, 期 -, 页码 9513-9525出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S210732
关键词
glioblastoma; miR-152-3p; SOS1; cisplatin
资金
- Medical Scientific Program of Shanghai Health and Family Planning Commission [201540163]
- Scientific Program of Jiangsu Province [BE2018643]
- Scientific Program of Changzhou [CJ20180029, CE20175025]
- 333 Projects of Jiangsu Scientific Research Program [BRA2018168]
- Scientific Program of Shandong Provincial Department of Education [J18KA254]
Background: Accumulating evidences suggest that microRNAs (miRNAs) play key roles in mediating glioblastoma progression. Decreased expression of miR-152-3p was reported in several cancer types including glioblastoma. Methods: The sensitivity of glioblastoma cells to cisplatin was assessed by the cell counting kit-8 assay and flow cytometry analysis. The expression of miR-152-3p was determined by RT-qPCR method. Bioinformatic analysis, dual luciferase reporter assay and Western blot were used to explore the target gene of miR-152-3p. The association between miR-152-3p and SOS1 was confirmed in glioblastoma tissues by Pearson correlation analysis. Results: In the current study, we discovered that overexpression of miR-152-3p increased cisplatin sensitivity while inhibition of miR-152-3p decreased cisplatin sensitivity in glioblastoma cells (T98G and U87). In addition, miR-152-3p augmented cell apoptosis induced by cisplatin treatment. It was further predicted and validated that SOS1, a protein involved in regulating chemotherapy sensitivity, was a direct target gene of miR-152-3p. SOS1 was proven to suppress the cytotoxic effect of cisplatin in glioblastoma. Transfection of recombinant SOS1 could effectively reverse the increased cisplatin sensitivity induced by miR-152-3p overexpression in T98G. Furthermore, overexpression of SOS1 reduced the percentage of apoptotic cells increased by miR-152-3p mimic in the presence of cisplatin in T98G. More importantly, a significant negative correlation between miR-152-3p levels and SOS1 levels was observed in glioblastoma tissues collected from 40 patients. Conclusion: Our study identified miR-152-3p as a chemotherapy sensitizer in glioblastoma.
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