MiR-296-3p inhibits cell proliferation by the SOX4-Wnt/β-catenin pathway in triple-negative breast cancer

• Published in: Journal of biosciences 2021-12, Vol.46 (4), Article 98
• Main Authors: Tian, Duo, Luo, Laifu, Wang, Tao, Qiao, Jian
• Format: Article
• Language: English
• Subjects: Adult; Anticancer properties; beta Catenin - genetics; beta Catenin - metabolism; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer; Cell Biology; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell proliferation; Cell Proliferation - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Life Sciences; Metabolic Networks and Pathways - genetics; Microbiology; MicroRNAs - genetics; Middle Aged; miRNA; Neoplasms; Plant Sciences; Proliferation; Regulatory mechanisms (biology); SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism; Stem cells; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumorigenesis; Wnt protein; Wnt Signaling Pathway; Wound healing; Zoology; β-Catenin
• ISSN: 0250-5991; 0973-7138; 0973-7138
• DOI: 10.1007/s12038-021-00219-6

MicroRNAs (miRNAs) have been demonstrated to play critical roles in the tumorigenesis of triple-negative breast cancer (TNBC). In this work, we addressed the sepecific role of miR-296-3p in TNBC. The levels of miR-296-3p and SOX4 were determined using RT-qPCR. The function of miR-296-3p overexpression on TNBC cell proliferation, migration, invasion, cancer stem cell (CSC)-like proterties, and Wnt pathway activation was investigated by MTT, EdU, wound healing, Transwell, sphere formation assays and western blot. Mechanistic investigations, including luciferase reporter, RNA pull-down, and RIP assays, were conducted to explore the regulatory mechanisms of miR-296-3p. We found that miR-296-3p was downregulated in TNBC tissues and cells. Overexpression of miR-296-3p suppressed TNBC cell proliferation, migration, invasion, and CSC-like proterties. Furthermore, miR-296-3p could bind to SOX4 and negatively modulate SOX4 expression. In addition, miR-296-3p was verified to inhibit Wnt/β-catenin pathway by downregulating SOX4. 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/β-catenin pathway by targeting SOX4 and exerts anti-tumor effects in TNBC.