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

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Abstract

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.

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Authors and Affiliations

  1. Department of General Surgery, Hefei BOE Hospital, Hefei, 230013, Anhui, China

    Duo Tian, Laifu Luo, Tao Wang & Jian Qiao

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  1. Duo Tian
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  2. Laifu Luo
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  3. Tao Wang
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  4. Jian Qiao
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Correspondence to Duo Tian.

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Communicated by Sorab Dalal.

Corresponding editor: Sorab Dalal

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Tian, D., Luo, L., Wang, T. et al. MiR-296-3p inhibits cell proliferation by the SOX4-Wnt/β-catenin pathway in triple-negative breast cancer. J Biosci 46, 98 (2021). https://doi.org/10.1007/s12038-021-00219-6

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