OncoTargets and Therapy (Nov 2019)
miR-152-3p Sensitizes Glioblastoma Cells Towards Cisplatin Via Regulation Of SOS1
Abstract
Meihua Wang,1,* Qi Wu,2,* Mingming Fang,3,* Wu Huang,4 Hong Zhu5 1Department of Pathology, Changzhou Tumor Hospital, Affiliated to Soochow University, Changzhou, People’s Republic of China; 2Department of Histology and Embryology, Heze Medical College, Heze, People’s Republic of China; 3Department of Radiotherapy, Changzhou Tumor Hospital, Affiliated to Soochow University, Changzhou, People’s Republic of China; 4Department of Neurosurgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 5Department of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wu HuangDepartment of Neurosurgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaEmail [email protected] ZhuDepartment of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, People’s Republic of ChinaEmail [email protected]: 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.Keywords: glioblastoma, miR-152-3p, SOS1, cisplatin
