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miR-125a-5p reverses epithelial-mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer.
- Source :
-
Molecular Medicine Reports . Nov2021, Vol. 24 Issue 5, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- MicroRNA (miR)-125a-5p represses tafazzin phospholipid-lysophospholipid transacylases (TAFAZZIN) expression and inhibits the epithelial-mesenchymal transition (EMT) of ovarian cancer cells. EMT was found to have a crucial role in the acquisition of chemoresistance. Thus, the present study aimed to determine whether miR-125a-5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer. The expression of miR-125a-5p/TAFAZZIN and its association with chemotherapy response were determined in tissue samples from patients with breast cancer. Furthermore, the effects of miR-125a-5p on breast cancer cells were elucidated using cell proliferation and cell apoptosis assays. Then, the regulatory mechanism of miR-125a-5p in breast cancer was investigated by reverse transcription-quantitative PCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that miR-125a-5p inhibited the EMT of MCF-7/adriamycin (Adr) breast cancer cells, as well as decreased the proliferation and increased the apoptosis of breast cancer cells treated with Adr/docetaxel. In addition, miR-125a-5p downregulated the expression levels of TAFAZZIN, Transglutaminase 2, phosphorylated-AKT, N-cadherin, vimentin and proliferating cell nuclear antigen, and significantly increased those of E-cadherin, cleaved caspase-3 and Bax in MCF7/Adr cells. Similar results were obtained with small interfering RNA-TAFAZZIN. Moreover, TAFAZZIN was identified as a direct target of miR-125a-5p in MCF7/Adr breast cancer cells. In addition, increased miR-125a-5p expression was observed in breast tumors from patients exhibiting a chemotherapy response, and TAFAZZIN mRNA expression was elevated in patients with no chemotherapy response. Hence, miR-125a-5p expression was negatively correlated with TAFAZZIN mRNA expression in breast cancer tissues. All these data suggested that miR-125a-5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer and, therefore, has potential as a novel therapeutic target for this disease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17912997
- Volume :
- 24
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Molecular Medicine Reports
- Publication Type :
- Academic Journal
- Accession number :
- 152764721
- Full Text :
- https://doi.org/10.3892/mmr.2021.12452