miR‑125a‑5p reverses epithelial‑mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer

Li,Dongmei; Chen,Limei; Zhang,Xiaofang; Wang,Yanhua; Huang,Chuansheng; Li,Jianglong; He,Feilong; He,Wenxing

doi:10.3892/mmr.2021.12452

miR‑125a‑5p reverses epithelial‑mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer

Authors:
- Dongmei Li
- Limei Chen
- Xiaofang Zhang
- Yanhua Wang
- Chuansheng Huang
- Jianglong Li
- Feilong He
- Wenxing He
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Affiliations: Breast Cancer Center, The Affiliated Cancer Hospital of Nanchang University (Jiangxi Provincial Cancer Hospital), Nanchang, Jiangxi 330029, P.R. China, Research Center for Differentiation and Development of TCM Basic Theory, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China
Published online on: September 20, 2021 https://doi.org/10.3892/mmr.2021.12452
Article Number: 812
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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