Abstract
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.
Highlights
Breast cancer (BC) is the second most common cancer worldwide and is the fifth major cause of cancerrelated deaths among women [1]
In order to explore the relationship between the microribonucleic acid- (miR-)210 expression and chemoresistance of breast cancer MCF-7 cells, the half maximal inhibitory concentration (IC50) of DDP on breast cancer MCF-7/DDP cells and control parental MCF-7 cells was detected through Cell Counting Kit-8 (CCK-8)
The relative expression level of miR-210 in the two cell lines was measured via quantitative polymerase chain reaction (qPCR), and it was found that the expression level of miR-210 in MCF-7/DDP cells was remarkably higher than that in control parental MCF-7 cells
Summary
Breast cancer (BC) is the second most common cancer worldwide and is the fifth major cause of cancerrelated deaths among women [1]. A recent report shows that breast cancer ranks first among young women aged 20-39 years old in terms of the number of new cases and death toll around the world [2]. Breast cancer is not a local tumor, but it involves lymph node or other organ metastasis leading to death. Comprehensive treatment based on surgery and chemotherapy is the main clinical treatment strategy for breast cancer. Chemotherapeutic drugs for breast cancer are still based on cisplatin (DDP) drugs. Despite the successful application of these drugs, the insensitivity of cancer to chemotherapeutic drugs in clinical application greatly reduces the efficacy of drugs and brings irresistible resistance to the treatment of patients’ diseases
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