Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway

The study is aimed at exploring the effect of microribonucleic acid- (miR-) 210 on the chemosensitivity of breast cancer and its potential molecular mechanism. Cell Counting Kit-8 (CCK-8) was applied to detect the half maximal inhibitory concentration (IC₅₀) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC₅₀ value of DDP on cells was detected via CCK-8 after downregulating the expression of miR-210 in MCF-7/DDP cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed the effect of themiR-210 downregulation on the apoptosis of drug-resistant MCF-7/DDP cells. Besides, the impacts of the miR-210 downregulation on apoptosis-related proteins and Janus-activated kinase- (JAK-) signal transducer and activator of transcription (STAT) signaling pathway-related proteins were examined by Western blotting. The interaction between miR-210 and the target protein was detected through luciferase activity assay, qPCR, and Western blotting. Drug-resistant MCF-7/DDP cells had significantly stronger resistance to DDP and a remarkably higher expression level of miR-210 than control parental MCF-7 cells (p < 0.05). After the downregulation of the miR-210 expression, MCF-7/DDP cells had markedly reduced resistance but obviously increased sensitivity to DDP (p < 0.05). MiR-210 downregulation increased the apoptosis of MCF-7/DDP cells (p < 0.05). In addition, after miR-210 was knocked down, the expression level of b-cell lymphoma 2 (Bcl-2) was decreased, while the expression levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate-specific proteinase-3 (caspase-3) were increased. Besides, miR-210 was able to suppress the expression of protein inhibitor of the activated STAT 4 (PIAS4) gene by directly targeting its 3' untranslated region (3'UTR). The expression of miR-210 has a correlation with chemoresistance of breast cancer MCF-7 cells. MiR-210 regulates the JAK-STAT signal transduction pathway by targeting PIAS4, thus exerting an effect on breast cancer chemosensitivity.