miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer
Sile Liu, Hongjing Zang, Hongmei Zheng, Weiyuan Wang, Qiuyuan Wen, Yuting Zhan, Yang� Yang, Yue Ning, Haihua Wang, Songqing Fan
Abstract
MicroRNA (miRNA) is involved in the physiological and pathological processes of various malignancies. In this study, miRNA microarray analysis showed that miR-4634 levels in A549 cells increased significantly after everolimus (RAD001) treatment. Decreased expression of miR-4634 was also found in non-small-cell lung carcinoma (NSCLC) cell lines and patients' tumors by qPCR. Additionally, a combination of miR-4634 and RAD001 exerted synergistic antitumor efficacy by inhibiting cell proliferation, migration, and colony formation. High expression of miR-4634 was significantly more common in non-cancerous lung tissue than adenocarcinoma or squamous cell carcinoma tissue (72.8%, 45.7%, and 50.9%, respectively; P < 0.001). Furthermore, high expression of miR-4634 was found to be more frequent in patients without lymph node metastasis (P = 0.037) by in-situ hybridization. Importantly, through univariate and multivariate analysis, high miR-4634 expression was associated with better prognosis of NSCLC patients. In conclusion, miR-4634 may act as a tumor suppressor in NSCLC, and to augment the efficacy of RAD001, co-treatment of miR-4634 and RAD001 might be a potential mTOR-targeted cancer therapy strategy for NSCLC patients. High expression of miR-4634 could be an independent good prognostic biomarker for NSCLC.