Hypoxia-Responsive Mir-301a and Mir-301b Promote Radioresistance of Prostate Cancer Cells via Downregulating NDRG2
Wei Wang, Mingbo Liu, Yawei Guan, Qingwu Wu
Department of Radiation Oncology, Henan Provincial People’s Hospital, Zhengzhou, Henan, China (mainland)
Med Sci Monit 2016; 22:2126-2132
MiR-301a and miR-301b are 2 oncomiRs involved in multiple types of cancer. In this study, we explored the expression change of miR-301a and miR-301b in prostate cancer cells in hypoxia and studied their regulation of autophagy and radiosensitivity of prostate cancer cells.
MATERIAL AND METHODS: QRT-PCR was performed to quantify the expression change of miR-301a and miR-301b in hypoxia. Their effects on autophagy were measured by Western blot analysis, and their effects on radiosensitivity were measured by clonogenic assay and flow cytometry. In addition, the regulation of miR-301a and miR-301b on NDRG2, a tumor-suppressor gene in prostate cancer, was also studied. The effect of miR-301a/b-NDRG2 axis on autophagy and radiosensitivity of prostate cancer cells was further investigated.
RESULTS: MiR-301a and miR-301b are 2 hypoxia responsive miRNAs that are significantly upregulated in hypoxia in prostate cancer cells. Higher level of miR-301a and miR-301b expression results in elevated autophagy and increased radioresistance in LNCaP cells. MiR-301a and miR-301b simultaneously target NDRG2 and decrease its expression. Knockdown of NDRG2 leads to increased autophagy and radioresistance.
CONCLUSIONS: MiR-301a and miR-301b are 2 hypoxia-responsive miRNAs that decrease autophagy of prostate cancer cells in hypoxia by targeting NDRG2. Through downregulating NDRG2, miR-301a and miR-301b can promote radioresistance of prostate cancer cells.
Keywords: Autophagy - genetics, Apoptosis - genetics, Cell Hypoxia - genetics, Cell Line, Tumor, Cell Proliferation - genetics, Down-Regulation, MicroRNAs - metabolism, Prostatic Neoplasms - radiotherapy, Radiation Tolerance, Tumor Suppressor Proteins - metabolism