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

• Published in: Aging (Albany, NY.) Vol. 8; no. 10; pp. 2509 - 2524
• Main Authors: Sun, Cheng-Cao, Li, Shu-Jun, Yuan, Zhan-Peng, Li, De-Jia
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 18.10.2016
• Subjects: 3' Untranslated Regions; Animals; Apoptosis - genetics; Cadherins - genetics; Cadherins - metabolism; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - physiology; DNA Damage; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Research Paper; RNA Interference; Signal Transduction - physiology; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; XPC; non-small cell lung cancer (NSCLC); microRNA-346 (miR-346); oncogenesis
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101080

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.