Bioinformatics identification of miR-514b-5p promotes NSCLC progression and induces PI3K/AKT and p38 pathways by targeting small glutamine-rich tetratricopeptide repeat-containing protein beta.

Abstract

Lung cancer is the most aggressive cancer with the highest mortality and incidence rates worldwide. MicroRNAs have been identified as potential targets for non-small cell lung cancer (NSCLC) treatment. However, the modulatory role of miR-514b-5p in NSCLC progression is little known. In the present study, miRNA expression datasets for NSCLC were downloaded from the Cancer Genome Atlas and Gene Ontology Omnibus databases. Gene expression was assessed using a quantitative real-time PCR, and western blot analysis and immunohistochemical staining was used to determine protein expression. Gain and loss of function experiments were performed to investigate the impact of miR-514b-5p and small glutamine-rich tetratricopeptide repeat-containing protein beta (SGTB) on cell proliferation and apoptosis. RNA immunoprecipitation and dual-luciferase assays were performed to analyse the target gene of miR-514b-5p. The biological roles of miR-514b-5p were lastly evaluated using nude mouse tumorigenicity assays in vivo. We found that miR-514b-5p was dramatically increased in NSCLC tissues and higher miR-514b-5p expression was associated with poorer overall survival in NSCLC patients. Furthermore, overexpression of miR-514b-5p promoted NSCLC cell growth and suppressed apoptosis by inducing the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT and p38 signalling pathways. Mechanistically, dual-luciferase and the RNA immunoprecipitation results highlighted that SGTB was a target gene of miR-514b-5p. Moreover, overexpression of SGTB reduced cell division and promoted apoptosis in vitro through blocking the PI3K/AKT and p38 signalling pathways. Our findings indicated that miR-514b-5p contributes to carcinoma progression in NSCLC via the PI3K/AKT and p38 signalling pathways by targeting SGTB and this could be a promising diagnostic and therapeutic target for the treatment of NSCLC.