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Research Paper Volume 8, Issue 10 pp 2509—2524
MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway
- 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China
- 2 Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P. R. China
- 3 Department of Toxicology, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China
Received: June 11, 2016 Accepted: October 4, 2016 Published: October 18, 2016
https://doi.org/10.18632/aging.101080How to Cite
Abstract
Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.