title: 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.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Tu
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Hui-Qiu
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Qi
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Xie
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D026362:Serum Response Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C476858:SRF protein, human; D026362:Serum Response Factor; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2