SRF-miR‑29b-MMP2 axis inhibits NSCLC invasion and metastasis.

Abstract	MicroRNAs play key roles in tumour metastasis. miR‑29b was previously reported to act as a tumour suppressor or an oncogene in diverse cancers. However, its accurate function and mechanism in metastasis of no-small cell lung cancer (NSCLC) are not well known. In this study, we describe the function of miR‑29b in NSCLC metastasis and its regulatory mechanisms. We found that miR‑29b is downregulated in high-metastatic NSCLC cells and low-expression of miR‑29b in primary NSCLC tissue was correlated with lymph node metastasis. Both gain- and loss-of-function study indicated overexpression of miR‑29b could suppress migration and invasion abilities of high-metastatic NSCLC cells, while downregulation of miR‑29b expression promoted migration and invasion of low-metastatic NSCLC cells in vitro. Moreover, introduction of miR‑29b inhibited high‑metastatic NSCLC cells, in vivo, metastasis to liver and lungs. Mechanistically, miR‑29b, induced by the transcription factor SRF, posttranscriptionally downregulates MMP2 expression by directly targeting its 3'-untranslated regions. These findings indicate a new regulatory mode, whereby miR‑29b, which is inhibited by its upstream transcription factor SRF, was able to promote its direct target MMP2 leading to NSCLC invasion and metastasis.
Authors	Hong-Yan Wang, Yong-Sheng Tu, Jie Long, Hui-Qiu Zhang, Cui-Ling Qi, Xiao-Bin Xie, Shu-Hua Li, Ya-Jie Zhang
Journal	International journal of oncology (Int J Oncol) Vol. 47 Issue 2 Pg. 641-9 (Aug 2015) ISSN: 1791-2423 [Electronic] Greece
PMID	26044095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	MIRN29a microRNA, human MicroRNAs SRF protein, human Serum Response Factor MMP2 protein, human Matrix Metalloproteinase 2
Topics	Animals Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology) Cell Line, Tumor Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms (genetics, pathology) Male Matrix Metalloproteinase 2 (genetics, metabolism) Mice MicroRNAs (genetics, metabolism) Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Serum Response Factor (genetics, metabolism)

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