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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 (IC(50)) of cisplatin (DDP) on cell, and quantit...

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Autores principales: Xing, Zeyu, Wang, Xin, Liu, Jiaqi, Liu, Gang, Zhang, Menglu, Feng, Kexin, Wang, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373480/
https://www.ncbi.nlm.nih.gov/pubmed/34423038
http://dx.doi.org/10.1155/2021/7703159
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author Xing, Zeyu
Wang, Xin
Liu, Jiaqi
Liu, Gang
Zhang, Menglu
Feng, Kexin
Wang, Xiang
author_facet Xing, Zeyu
Wang, Xin
Liu, Jiaqi
Liu, Gang
Zhang, Menglu
Feng, Kexin
Wang, Xiang
author_sort Xing, Zeyu
collection PubMed
description 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 (IC(50)) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC(50) 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.
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spelling pubmed-83734802021-08-19 Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway Xing, Zeyu Wang, Xin Liu, Jiaqi Liu, Gang Zhang, Menglu Feng, Kexin Wang, Xiang Biomed Res Int Research Article 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 (IC(50)) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC(50) 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. Hindawi 2021-08-11 /pmc/articles/PMC8373480/ /pubmed/34423038 http://dx.doi.org/10.1155/2021/7703159 Text en Copyright © 2021 Zeyu Xing et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xing, Zeyu
Wang, Xin
Liu, Jiaqi
Liu, Gang
Zhang, Menglu
Feng, Kexin
Wang, Xiang
Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title_full Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title_fullStr Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title_full_unstemmed Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title_short Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway
title_sort effect of mir-210 on the chemosensitivity of breast cancer by regulating jak-stat signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373480/
https://www.ncbi.nlm.nih.gov/pubmed/34423038
http://dx.doi.org/10.1155/2021/7703159
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