MiR-101-3p Inhibits the Growth and Metastasis of Non-Small Cell Lung Cancer Through Blocking PI3K/AKT Signal Pathway by Targeting MALAT-1

Background: MiR-101-3p is an important tumor suppressor miRNA in many human cancers. This study was to investigate the role of miR-101-3p in the progression of non-small cell lung cancer (NSCLC) and its potential underlying mechanism.Methods: In this study, the endogenous expression of miR-101-3p or MALAT-1 in cells was modulated by cell transfection assays. The regulatory interaction of miR-101-3p and MALAT-1 was examined by Luciferase reporter gene and RNA pull-down assays. The effect of miR-101-3p or MALAT-1 on NSCLC cells was evaluated by cell proliferation assays, wound-healing assays and transwell invasion assays. The mice tumor model was established to test the role of miR-101-3p and MALAT-1 in the growth and metastasis of NSCLC in vivo.Results: The relative expression of miR-101-3p in NSCLC cells was significantly decreased; while MALAT-1 was significantly increased. Moreover, overexpression of miR-101-3p could significantly inhibit the proliferation, migration and invasion of NSCLC cells in vitro, as well as MALAT-1 expression. Further studies confirmed that miR-101-3p could specifically repress MALAT-1 expression through direct binding; MALAT-1 overexpression completely reversed the miR-101-3p-induced suppression on the viability, migration and invasion of NSCLC cells and MALAT-1 expression. Finally, we confirmed that miR101-3p could block the MALAT-1-induced activation of PI3K/AKT signal pathway and resulted in the inhibition on the growth and metastasis of NSCLC cells in vivo.Conclusion: MiR-101-3p inhibited the growth and metastasis of NSCLC through blocking PI3K/AKT signal pathway by targeting MALAT-1. (C) 2017 Elsevier Masson SAS. All rights reserved.