miR-631 suppresses oncogene RAB11A in oral squamous cell carcinoma

Abstract

Despite technological advancements, the five-year survival rate for oral squamous cell carcinoma (OSCC) remains dismally low. To develop more effective therapies, we intended to identify the potential therapeutic tumor suppressor microRNAs in OSCC. Previously, a microRNA microarray analysis of 5-Azacytidine treated SCC131 cells had identified 50 upregulated miRs. Of these, miR-631 that had no previously known roles in OSCC was selected for further analysis in the present study. We show that miR-631 binds directly to the oncogene RAB11A and reduces its transcript and protein levels. The upregulation of miR-631 occurs due to its gene promoter demethylation after 5-Azacytidine treatment. We demonstrate that miR-631 reduces proliferation and anchorage-independent growth of OSCC cells in soft agar and promotes apoptosis, in part, via targeting RAB11A. An inverse relationship between miR-631 and RAB11A levels observed across multiple cancer cell lines and in 58.33% of OSCC patient samples highlights the biological significance of their interaction. Further, miR-631 and RAB11A interaction reduces the Wnt signaling in OSCC. Additionally, the nude mice OSCC xenograft study proves the tumor suppressive nature of miR-631. Based on our results, we propose that miR-631 holds promise as a potential therapeutic agent for treating OSCC.