microRNAs in oral cancer: Moving from bench to bed as next generation medicine

Oral cancer is the thirteenth most common cancer in the world, with India contributing to 33% of the global burden. Lack of specific non-invasive markers, non-improvement in patient survival and tumor recurrence remain a major clinical challenge in oral cancer. Epigenetic regulation in the form of microRNAs (miRs) that act as tumor suppressor miRs or oncomiRs has gained significant momentum with the advancement in the field, suggesting the potential for clinical application of miRs in oral cancer. The current review of literature identified miR-21, miR-27a(-3p), miR-31, miR-93, miR-134, miR-146, miR-155, miR-196a, miR-196b, miR-211, miR-218, miR-222, miR-372 and miR-373 to be up-regulated and let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, miR-26a, miR-99a-5p, miR-137, miR-139-5p, miR-143-3p, miR-184 and miR-375 to be down-regulated in oral cancer. Mechanistic studies have uncovered several miRs that are deregulated at varying levels and in different stages of oral cancer progression, thus providing clinical utility in better diagnosis as well as usefulness in prognosis by identifying patients with poor prognosis or stratifying patients based on responsiveness to chemoand radio-therapy. Lastly, exogenous modulation of miR expression using miRNA-based drugs in combination with first-line agents may be adopted as a new therapeutic modality to treat oral cancer. Knowledge of miRs and their involvement in key molecular processes, clinical association, responsiveness to therapy and clinical advancement may highlight additional avenues in order to improve patient morbidity and mortality. Furthermore, combinatorial approaches with miR-therapy may be efficacious in oral cancer.