MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis.

Abstract

MicroRNAs (miRNAs) have important roles in various cancers, including non-small cell lung cancer (NSCLC). Although several miRNAs have reported to be involved in the development of NSCLC, understanding the regulatory roles of other miRNAs in NSCLC is essential. Therefore, the aim of the current study was to explore the roles and mechanisms of screened miRNAs in NSCLC. First, the differentially expressed miRNAs that were screened based on GSE29248 microarray data retrieved from Gene Expression Omnibus (GEO). The expression of miR-92a, acted as an oncogene in many cancers, was validated using quantitative real-time PCR (qRT-PCR), and then its association with overall survival was analyzed. The efficacy of miR-92a to promote cell proliferation, invasion and metastasis was evaluated invitro, and invivo. Then, the role of miR-92a in epithelial-mesenchymal transition (EMT), a key step of the progression of tumor cell metastasis, was investigated in NSCLC cells. The association of miR-92a and its downstream target was investigated in both cell line and clinical specimens. Furthermore, gain- and loss-of-function studies of the phosphatase and tensin homolog (PTEN) were performed to assess whether the effect of miR-92a promoted growth and metastasis of NSCLC cells were via targeting PTEN. Our results showed that miR-92a was significantly upregulated in NSCLC tissues and NSCLC cell lines, and was positively associated with poor prognosis of NSCLC patients. The overexpression of miR-92a enhanced EMT-relatived protein levels, promoted NSCLC cell migration and invasion invitro, and increased tumor growth invivo. Bioinformatic prediction and function assay suggested that PTEN, a negative regulator of PI3K/AKT pathway, was a direct target of miR-92a. It was found that PTEN expression was inversely correlated with miR-92a in NSCLC tissues. In addition, miR-92a could activate the PI3K/AKT pathway by inhibiting PTEN expression. Notably, Transwell and wound healing assays demonstrated that altering PTEN expression abrogated the promotive effects of miR-92a on NSCLC cell migration and invasion. Taken together, these results demonstrated that miR-92a induced EMT and regulated cell migration and invasion in the NSCLC cells through regulating PI3K/AKT signaling pathway by targeting PTEN, indicating that miR-92a may be an attractive target and prognostic marker for NSCLC.