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MicroRNAs (miRNAs) have been demonstrated to play critical roles in the tumorigenesis of triple-negative breast cancer (TNBC). In this work, we addressed the specific role of miR-296-3p in TNBC. The levels ofmiR-296-3p and SOX4 were determined using RT-qPCR. The function of miR-296-3p overexpression onTNBC cell proliferation, migration, invasion, cancer stem cell (CSC)-like properties, and Wnt pathwayactivation was investigated by MTT, EdU, wound healing, Transwell, sphere formation assays and westernblot. Mechanistic investigations, including luciferase reporter, RNA pull-down, and RIP assays, were conductedto explore the regulatory mechanisms of miR-296-3p. We found that miR-296-3p was downregulatedin TNBC tissues and cells. Overexpression of miR-296-3p suppressed TNBC cell proliferation, migration,invasion, and CSC-like properties. Furthermore, miR-296-3p could bind to SOX4 and negatively modulateSOX4 expression. In addition, miR-296-3p was verified to inhibit Wnt/beta-catenin pathway by downregulatingSOX4. Moreover, overexpression of SOX4 or activation of Wnt pathway rescued the miR-296-3p upregulation-mediated suppressive effect on cellular processes in TNBC. In conclusion, miR-296-3p inhibits Wnt/beta-catenin pathway by targeting SOX4 and exerts anti-tumor effects in TNBC.
Volume 48, 2023
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