miR-127-3p Inhibits Cell Stemness and Docetaxel Resistance in Triple-Negative Breast Cancer by Targeting KIF3B

miR-127-3p通过靶向KIF3B抑制三阴性乳腺癌细胞的干性和多西他赛耐药性

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作者:Zi-Chao He,Jun-Jie Zhao,Ting Yan

Abstract

This study investigated the mechanism of miR-127-3p in tumor cell stemness and docetaxel (DTX) resistance in triple-negative breast cancer (TNBC). hsa-miR-127-3p and KIF3B levels were predicted using databases and validated in TNBC and paracancerous tissues. KM survival curves were plotted to analyze the effect of miR-127-3p on patient survival. Pearson's analysis was used to determine the correlation between miR-127-3p and KIF3B mRNA in cancer tissues. Drug-resistant TNBC cell lines were established. After transfection, the cell viability, IC50, proliferation, migration, invasion, DTX resistance, apoptosis, and expression of the stemness markers SOX2, OCT4, and Nanog were detected. Databases were used to predict the downstream targets of miR-127-3p. The starBase database and dual-luciferase assay were used to predict and validate the binding relationship of miR-127-3p with KIF3B. Finally, the effect of miR-127-3p on transplanted tumors in TNBC nude mice was verified. miR-127-3p was expressed at low levels in TNBC tissues and was notably associated with shorter survival. Upregulation of miR-127-3p reduced TNBC cell stemness and DTX resistance. miR-127-3p targeted KIF3B. KIF3B overexpression averted the effect of miR-127-3p. miR-127-3p inhibited the growth of transplanted tumors in TNBC nude mice. Overall, miR-127-3p targets KIF3B, thereby reducing TNBC cell stemness and reversing DTX resistance.

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