Journal
AGING-US
Volume 8, Issue 10, Pages 2509-2524Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101080
Keywords
microRNA 346 (miR-346); XPC; non-small cell lung cancer (NSCLC); oncogenesis
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Funding
- National Natural Science Foundation of China [81271943]
- plan for Scientific and Technological Innovation Team of High-tech Industries of Wuhan Municipal Science and Technology Bureau [2015070504020219]
- Fundamental Research Funds for the Central Universities [2015305020202]
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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.
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