miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer.

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.

Citation

Sile Liu, Hongjing Zang, Hongmei Zheng, Weiyuan Wang, Qiuyuan Wen, Yuting Zhan, Yang Yang, Yue Ning, Haihua Wang, Songqing Fan. miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer. Scientific reports. 2020 Aug 04;10(1):13079

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PMID: 32753611

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