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.