MiR-340-5p affects oral squamous cell carcinoma (OSCC) cells proliferation and invasion by targeting endoplasmic reticulum stress proteins

Abstract

Lip and oral cancer is the 12th most common malignancy and oral squamous cell carcinoma (OSCC) represents about 90% of all oral malignant tumors, with an annual mortality rate exceeding 50%. Recent studies have concluded that endoplasmic reticulum stress may have a close link to tumor genesis, progression, and prognosis. As an epigenetic regulatory factor, miRNA exerts a substantial effect on tumor development. This study found that transcription factor 6 (ATF6) and Protein kinase R-like endoplasmic reticulum kinase (PERK) were abnormally increased within OSCC tissue samples and oral cancer cell lines. The biological functions of ATF6 and PERK within CAL-27 and SCC-9 oral cancer cell lines were investigated. In vitro experiments revealed that silencing ATF6 and PERK suppressed the ability of cells to proliferate and to invade and mitigated cell endoplasmic reticulum (ER) stress. As predicted by bioinformatics analyses and experiments, miR-340-5p could simultaneously bind to ATF6 and PERK 3′ untranslated region (UTR) and inhibit ATF6 and PERK expression. miR-340-3p overexpression inhibited while down-regulation of miR-340-5p boosted the invading and proliferating ability of oral cancer cells, and miR-340-3p also affects ER stress. When co-transfected in oral cancer cells, dynamic effects of miR-340-5p and its targets PERK and ATF6 on cell phenotypes in vitro and in vivo were investigated. PERK or ATF6 overexpression dramatically attenuated phenotypes of miR-340-5p up-regulation. Altogether, miR-340-5p targets the endoplasmic reticulum stress proteins PERK and ATF6 to affect OSCC cell proliferation and invasion.