The Roles Of MiRNA-106b/93 In Cisplatin Sensitivity Of Cervical Cancer

Cervical carcinoma is the second most common cancer among female worldwide, only secondary to breast cancer. Persistent infection of high-risk HPV (human papilloma virus) is considered to be the leading cause of carcinogenesis, with high-risk HPV-16 and HPV-18 accounting for approximately 70% of all cervical cancers. Cisplatin is the first-line chemotherapeutics for various tumors and often clinically unavoidable cisplatin resistance leads to treatment failure. Accumulating evidences suggest that microRNA involved in the regulation of chemotherapy sensitivity in cancer. miR-106b/93, belong to miR-106b-93-25 cluster, exert as oncogene in multiple malignancies. However, the role of miR-106b/93 in cervical cancer is unknown. Using Q-PCR, we found that the expression of miR-106b, miR-93 and miR-25 in cervical tumor tissues and cervical cancer cell lines is relatively higher than normal cervix. Further, expression of miR-106b/93 had reverse correlation with sensitivity to cisplatin in HPV (+) cervical cancer cell lines HeLa (HPV 18+) and CaSki (HPV 16+). miR-106b, miR-93 and miR-25 was downregulated after treatment with cisplatin in HeLa and CaSki. Overexpression of miR-106b/93 resulted in reduced cisplatin sensitivity of HeLa and CaSki; on the contrary, abrogation of miR-106b/93 increased cisplatin sensitivity in HeLa and CaSki. We verified that miR-106b/93 decreased cisplatin sensitivity via promoting proliferation and inhibiting apoptosis induced by cisplatin in HeLa cells. Additionally, we found that miR-106b/93 mediated cisplatin resistance in cervical cancer through degradation of RAD1 and TP53INP1. Reverse correlationship of miR-106b/93 and RAD1, TP53INP1 was observed both in expression patten and role in cisplatin sensitivity in cervical cancer, which was consist with our hypothesis. Taken together, elevated miR-106b/93 in cervical cancer contributes to cisplatin-based chemo-resistance via targeting RAD1 and TP53INP1. This study provides new insight into the role of miR-106b and miR-93 in carcinogenesis and miR-106b/93 can be potential target for combinational treatment.