Long non-coding RNA TRPM2-AS sponges microRNA-138-5p to activate epidermal growth factor receptor and PI3K/AKT signaling in non-small cell lung cancer

Background: Long non-coding RNAs (lncRNAs) can play pivotal roles in tumor progression by acting as microRNA (miRNA) sponges. This study aimed to investigate the association of a novel lncRNA, TRPM2-AS, with the miR-138-5p/EGFR axis in the development of non-small cell lung cancer (NSCLC). Methods: Sixty NSCLC tissues and paired adjacent non-tumor tissues were analyzed. The relative expression levels of TRPM2-AS, miR138-5p, and epidermal growth factor receptor (EGFR) and the interactions between them were analyzed. The NSCLC cell lines NCI-H1299 and A549 were transfected with TRPM2-AS shRNA/pc DNA, and miR-138- 5p mimics. Cell proliferation, migration, invasion, and apoptosis were examined in response to different transfection conditions. Dual-luciferase reporter assay was performed to identify the target interactions between TRPM2-AS, miR-138-5p, and EGFR. A549 cells stably transfected with shRNA were injected into BALB/c null nude mice to establish a tumor xenograft model. Results: TRPM2-AS was up-regulated in NSCLC tumors and cell lines. Cell proliferation, migration, and invasion were inhibited in NSCLC cells treated with sh-TRPM2-AS, while apoptosis was induced. The targeting of TRPM2-AS by miR138-5p and miR138-5p by EGFR were validated with dual-luciferase reporter assay. TRPM2-AS was found to be negatively correlated with miR138-5p but positively correlated with EGFR. PI3K/AKT/mTOR was activated by pcDNA-EGFR but inactivated by miR-138-5p mimics. In the tumor xenograft mouse model, sh-TRPM2-AS suppressed tumor formation, reduced the expression of EGFR and Ki67, and promoted tumor cell apoptosis. Conclusions: Our results suggested that TRPM2-AS can increase the levels of EGFR via sponging miR138-3p; this promoted NSCLC cell proliferation, migration, and invasion in vitro, and exacerbated tumors in vivo. These findings highlight TRPM2-AS/miR-138-5p as a potential target for reducing drug resistance in patients with NSCLC.