MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36

• Published in: OncoTargets and therapy Vol. 13; pp. 769 - 782
• Main Authors: Xia, Wenfei, Liu, Yun, Du, Yaying, Cheng, Teng, Hu, Xiaopeng, Li, Xingrui
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Dove
• Subjects: Breast cancer; Cancer cells; Drug resistance; Drug therapy; Genes; Genetic research; Infection; Journalists; Luciferase; Messenger RNA; MicroRNA; Original Research; RNA; Tumors; Vincristine; Canada; China; breast cancer; ZFP36; miR-423; Wnt/β-catenin; micro RNAs
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/ott.s217745

The effects of microRNA-423 on proliferation and drug resistance of breast cancer cells were explored, the downstream target genes of miR-423 and the targeted regulatory relationship between them were studied. RT-qPCR was used to detect the expression of miR-423 in breast cancer tissues and cell lines, and the transfection efficiency of miR-423 inhibitory vector miR-423-inhibitor was constructed and verified. CCK-8 and colony formation assays were used to examine the effect of miR-423 on tumor cell proliferation. Target gene prediction and screening and luciferase reporter assay were used to verify downstream target genes of miR-432. The mRNA and protein expression of miR-423target gene ZFP36 was detected by RT-qPCR and Western blotting. The expression of miR-423 was significantly higher than that in normal tissues. Compared to the non-malignant mammary epithelial cell line MCF-10A, the expression of miR-423 was significantly raised in MCR-7 and MCF-7/ADR cells. ZFP36 was a downstream target gene of miR-423 and negatively correlated with the expression of miR-423 in breast cancer. The knockdown of miR-423 can significantly enhance the cytotoxicity of the drug, increase the apoptotic rate of MCF-7/ADR cells. miR-423 was capable of activating the Wnt/β-catenin signaling pathway leading to chemoresistance and proliferation, whereas overexpression of ZFP36 reduced drug resistance and proliferation. miR-423 acted as an oncogene to promote tumor cell proliferation and migration. ZFP36 was a downstream target gene of miR-423, and miR-423 inhibited the expression of ZFP36 via Wnt/β-catenin signaling pathway of breast cancer cells.