Abstract 953: miR-31 targets ARID1A to enhance the progression of oral carcinoma

Abstract

Abstract miR-31 is an oncogenic microRNA in several malignancies including oral squamous cell carcinoma (OSCC). However, the function of miR-31 in modulating the stem cell properties in OSCC has not yet been explored. AT-rich interacting domain (ARID) containing protein members play pluripotent roles in modulating chromatin accessibility of the transcription machineries for gene expression. ARID1A has been shown suppressive to several malignancies and the driver mutations in ARID1A gene are noted in tumors. In this study, we identified that miR-31 targets ARID1A in OSCC, and a reverse expression between miR-31 and ARID1A was noted in OSCC tumors. Furthermore, the miR-31 induced migration, invasion, CSC cell population and stemness gene expression were rescued by ARID1A expression in OSCC cells. ARID1A suppressed the transcription activity of a panel of stemness markers through its affinity to A-T rich region in the promoters. A reverse correlation between ARID1A and these stem cell markers was also seen in OSCC tumors. miR-31+/ARID1A− OSCC cell subclone exhibited higher potency in sphere formation, as well as tumorigenesis and neck metastasis in nude mice relative to other cell subclones. In addition, tumors carrying high miR-31 expression and low ARID1A expression had the worst survival. In summary, this study provides novel mechanistic clues demonstrating that miR-31 targets ARID1A to enrich the stemness properties for OSCC progression. Citation Format: Wen-Cheng Lu, Shu-Chun Lin, Kuo-Wei Chang. miR-31 targets ARID1A to enhance the progression of oral carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 953.