Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA playing oncogenic role in several cancers, including cervical cancer. However, its role in radiosensitivity of cervical cancer is not yet well understood. This study explored the role of MALAT1 in radiosensitivity of high-risk human papillomavirus (HR-HPV)-positive cervical cancer and whether there is a ceRNA mechanism which participated in its regulation over radiosensitivity. Based on tissue samples from 50 cervical cancer cases and 25 healthy controls, we found MALAT1 expression was significantly higher in radioresistant than in radiosensitive cancer cases. In addition, MALAT1 and miR-145 expression inversely changed in response to irradiation in HR-HPV+ cervical cancer cells. By using clonogenic assay and flow cytometry analysis of cell cycle distribution and apoptosis, we found CaSki and Hela cells with knockdown of MALAT1 had significantly lower colony formation, higher ratio of G2/M phase block and higher ratio of cell apoptosis. By performing RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay, we confirmed that miR-145 and MALAT1 were in the same Ago2 complex and there was a reciprocal repression between them. Then, we explored the function of MALAT1-miR-145 in radiosensitivity of cervical cancers cells and demonstrated that si-MALAT1 and miR-145 had some level of synergic effect in reducing cancer cell colony formation, cell cycle regulation, and inducing apoptosis. These findings provide an important clue about microRNA-lncRNA interaction in the mechanism of radioresistance of cervical cancer.