Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

Abstract

Long non‑coding RNA SLC25A25 antisense RNA 1 (SLC25A25‑AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25‑AS1 is implicated in the aggressiveness of non‑small cell lung cancer (NSCLC) and the possible under‑ lying mechanism. SLC25A25‑AS1 expression in NSCLC was determined by reverse transcription‑quantitative PCR. The proliferation, apoptosis, migration and invasion of NSCLC cells were tested in vitro through cell counting kit‑8 assay, flow cytometry analysis, Transwell migration and invasion assays, followed by in vivo validation using animal experiments. Additionally, the competitive endogenous RNA theory for SLC25A25‑AS1, microRNA‑195‑5p (miR‑195‑5p) and inte‑ grin α2 (ITGA2) was identified using subcellular fractionation, bioinformatics analysis, reverse transcription‑quantitative PCR, western blotting, a luciferase assay and RNA immu‑ noprecipitation. As compared with normal lung tissues, increased expression of SLC25A25‑AS1 was demonstrated in NSCLC tissues using The Cancer Genome Atlas database.. In addition, SLC25A25‑AS1 was overexpressed in both NSCLC tissues and cell lines. High SLC25A25‑AS1 expres‑ sion was markedly associated with shorter overall survival time of patients with NSCLC. SLC25A25‑AS1 silencing impeded NSCLC cell proliferation and triggered apoptosis, while restricting cell migration and invasion. Tumour growth in vivo was also impaired by SLC25A25‑AS1 silencing. Mechanistically, SLC25A25‑AS1 was demonstrated to be an miR‑195‑5p sponge in NSCLC cells. miR‑195‑5p mimics decreased ITGA2 expression in NSCLC cells by directly targeting ITGA2, and SLC25A25‑AS1 interference decreased ITGA2 expression by sequestering miR‑195‑5p. Furthermore, the antitumour effects of SLC25A25‑AS1 silencing on malignant behaviours were counteracted when ITGA2 was restored or when miR‑195‑5p was silenced. In summary, by controlling the miR‑195‑5p/ITGA2 axis, SLC25A25‑AS1 served tumour‑promoting roles in NSCLC cells. Therefore, the SLC25A25‑AS1/miR‑195‑5p/ITGA2 signalling pathway might be an attractive target for future therapeutic options in NSCLC.