BMSCs-Derived Exosomal MiR-126-3p Inhibits the Viability of NSCLC Cells by Targeting PTPN9.

Abstract

Purpose: Recent studies have manifested that bone marrow mesenchymal stem cells (BMSCs) derived exosomes affect the progression of tumors through carrying endogenous molecules. To explore the role of BMSCs-derived exosomes carrying abundant micro ribonucleic acid (miR)-126-3p in non-small-cell lung cancer (NSCLC).

Methods: Firstly, A549 cells were transfected with miR-126-3p to detect the role of miR-126-3p in A549 cells. Next, miR-126-3p was transfected into BMSCs, and BMSCs-derived exosomes with over-expressed miR-126-3p (Exo-miR-126-3p) were isolated through ultracentrifugation. After that, A549 cells were co-incubated with Exo-miR-126-3p to determine the effects of Exo-miR-126-3p on cell proliferation, migration, invasion, and apoptosis. Besides, the targeted relationship between miR-126-3p and protein tyrosine phosphatase non-receptor type 9 (PTPN9) was confirmed via bioinformatics analysis and dual-luciferase reporter gene analysis. Western blotting (WB) was employed to measure the expressions of PTPN9 and related proteins in A549 cells. Additionally, the effects of over-expressed miR-126-3p derived from BMSCs exosomes on tumor growth and apoptosis of NSCLC cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo.

Results: Overexpressed miR-126-3p suppressed the viability, migration, and invasion of A549 cells in vitro. Based on the results of exosome content analysis, miR-126-3p could mediate the inhibitory effect of exosomes on A549 cells by negative regulation of PTPN9. Notably, over-expressed miR-126-3p derived from BMSCs inhibited the tumor growth and apoptosis in vivo.

Conclusions: Taken together, the key finding of the study indicated that over-expressed BMSCs-derived exosomal miR-126-3p can suppress the progression of NSCLC through negatively regulating PTPN9.