Upregulation of microRNA‑181a‑5p increases the sensitivity of HS578T breast cancer cells to cisplatin by inducing vitamin D receptor‑mediated cell autophagy

Lin,Jianmin; Chen,Xuming; Sun,Mingliang; Qu,Xiaojiao; Wang,Ye; Li,Chenxi; Li,Xiujuan; Zhao,Li; Su,Zhiying; Ye,Huiming

doi:10.3892/ol.2021.12508

April-2021 Volume 21 Issue 4

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April-2021 Volume 21 Issue 4

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Upregulation of microRNA‑181a‑5p increases the sensitivity of HS578T breast cancer cells to cisplatin by inducing vitamin D receptor‑mediated cell autophagy

Authors:
- Jianmin Lin
- Xuming Chen
- Mingliang Sun
- Xiaojiao Qu
- Ye Wang
- Chenxi Li
- Xiujuan Li
- Li Zhao
- Zhiying Su
- Huiming Ye
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Affiliations: Department of Clinical Laboratory, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, Department of Surgery, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, Department of Cardiac Surgery, Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, Department of Immunology, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China

Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 247
|
Published online on: February 3, 2021

https://doi.org/10.3892/ol.2021.12508
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Abstract

Breast cancer (BC) is the leading cause of death in females worldwide. Although cisplatin is a strong‑effect and broad‑spectrum chemotherapy drug, resistance to cisplatin remains a significant factor effecting clinical efficacy. The underlying mechanism of cancer cell resistance to cisplatin is not fully understood. MicroRNAs (miRs/miRNAs), as a regulator, are involved in regulating chemosensitivity to numerous chemotherapeutic drugs. The present study aimed to investigate the function of miR‑181a‑5p as a potential tumor suppressor in improving the efficiency of cisplatin in BC. The IC₅₀ of cisplatin and miR‑181a‑5p expression were determined in five BC cell lines, and HS578T was selected as an appropriate cell line for subsequent experiments. The sensitivity of HS578T cells to cisplatin was assessed using cell proliferation, migration and apoptosis assays. Western blotting was performed to detect the expression of vitamin D receptor (VDR) and autophagy in HS578T cells. It was found that the increase in autophagy resulted in increased apoptosis and sensitivity to cisplatin in HS578T cells. miR‑181a‑5p transfection also inhibited the proliferation and migration ability of HS578T cells and induced apoptosis. Meanwhile, HS578T cells have increased sensitivity to cisplatin. VDR, as a target gene and autophagy regulator of miR‑181a‑5p, was negatively regulated by miR‑181a‑5p. Upon the decrease in VDR expression, the autophagy in HS578T cells was increased. These results indicate that the increase in autophagy enhanced the chemosensitivity of cisplatin by inducing apoptosis of HS578T cells and by inhibiting proliferation and migration. The present study showed that miR‑181a‑5p increased the chemical sensitivity of HS578T cells to cisplatin by inhibiting VDR to promote autophagy. The use of miR‑181a‑5p/autophagy/VDR‑based treatment strategies may be a potential method to overcome cisplatin resistance in BC.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Upregulation of microRNA‑181a‑5p increases the sensitivity of HS578T breast cancer cells to cisplatin by inducing vitamin D receptor‑mediated cell autophagy

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