miR-631 targets the oncogene RAB11A : implications for oral squamous cell carcinoma pathogenesis and therapeutics

Despite technological advancements, the five-year survival rate for oral squamous cell carcinoma (OSCC) remains low, highlighting the urgent need to develop more effective therapies. With this objective, we intended to identify the potential therapeutic tumor suppressor microRNAs (miRs) in OSCC. In a previous work from our laboratory, we treated OSCC cells with 5-Azacytidine, a global DNA methyltransferase inhibitor, and subsequently performed a microRNA microarray analysis and identified 50 upregulated miRs. Of these, miR-631 that had no previously known roles in OSCC was selected for the further analysis in the present study. Our experiments show that miR-631 reduces proliferation of OSCC cells and binds to the 3’UTR of the oncogene RAB11A and reduces its expression at both the transcript and protein levels. The upregulation of miR-631 is shown to be due to its promoter demethylation after the 5-Azacytidine treatment. We demonstrate that miR-631 inhibits proliferation and anchorage-independent growth in soft agar and increases apoptosis of OSCC cells, in part, via targeting RAB11A . The inverse correlation in the levels of miR-631 and RAB11A in various cancer cell lines and in a majority (58.33%) of OSCC patient samples suggests the biological relevance of their interaction. The nude mice OSCC xenograft study suggests the tumor suppressive nature of miR-631. Further, miR-631 and RAB11A interaction reduces the Wnt signaling in OSCC. Based on our results, we propose that miR-631 functions as a tumor suppressor and holds promise as a potential therapeutic agent for treating OSCC.