Metformin Regulates the Proliferation and Motility of Melanoma Cells by Modulating the LINC00094/miR-1270 Axis

Abstract

Background Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear. Methods We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays. Results We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher LINC00094 levels in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissue. A marginal association was observed between elevated LINC00094 expression and poor overall survival in nondiabetic patients with melanoma. Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that LINC00094 silencing inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis revealed G1 phase arrest following LINC00094 knockdown, with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Conclusions Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, indicating its therapeutic potential in melanoma treatment.