TY - JOUR T1 - MiR-146a-dependent regulation of CD24/AKT/β-catenin axis drives stem cell phenotype in oral cancer JF - bioRxiv DO - 10.1101/429068 SP - 429068 AU - Sangeeta Ghuwalewala AU - Dishari Ghatak AU - Sumit Das AU - Pijush Das AU - Ramesh Butti AU - Mahadeo Gorain AU - Gopal C Kundu AU - Susanta Roychoudhury Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/27/429068.abstract N2 - Cancer stem cells (CSCs) are known to potentiate tumor initiation and maintenance in oral squamous cell carcinoma (OSCC). Increasing evidences suggest that CD44highCD24low population in OSCC exhibit CSC-like characteristics. The role of mi-RNAs in maintenance of oral CSCs has remained unclear. Here we report that CD44highCD24low population within OSCC cell lines and primary HNSCC tumors have an elevated expression of miR-146a. Moreover, over-expression of miR-146a results in enhanced stemness phenotype by augmenting CD44highCD24low population. We demonstrate that miR-146a induces CSC property by stabilizing β-catenin with concomitant loss of E-cadherin and CD24. Interestingly, CD24 has been identified as a novel functional target of miR-146a and ectopic expression of CD24 abrogates miR-146a driven potential CSC phenotype. Mechanistic analysis reveals that higher CD24 levels inhibit AKT phosphorylation leading to β-catenin degradation in non-CSCs. We also validate that the miR-146a/CD24/AKT loop significantly alters tumorigenic ability in vivo. Furthermore, we confirmed that β-catenin trans-activates miR-146a, thereby forming a positive feedback loop contributing to stem cell maintenance. Collectively, our study demonstrates that miR-146a regulates CSC-driven properties in OSCC through CD24-AKT-β-catenin axis. ER -