MiR-183 promotes radioresistance of lung adenocarcinoma H1299 cells via epithelial-mesenchymal transition.

Yi Huang,Ze Yang,Yuju Bai,Yuanyan Wang,Hu Ma,Mengmei Zhang,Wenjing Geng,Jihang Luo,Yang Li

doi:10.1590/1414-431x20209700

Abstract

Lung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.

Highlights

Radiation therapy is considered one of the main treatment strategies for lung adenocarcinoma
The results revealed that miR183 was highly expressed in H1299R cells, suggesting that miR-183 played an important role in the maintenance of radioresistance in lung adenocarcinoma H1299 cells
We detected the expression of zinc finger E-box-binding homeobox 1 (ZEB1) and epithelial-mesenchymal transition (EMT)-related markers in H1299 and H1299R cells by quantitative polymerase chain reaction (qPCR) and western blotting

Summary

Introduction

Radiation therapy is considered one of the main treatment strategies for lung adenocarcinoma. During radiotherapy, some tumor cells are tolerant to radiation, reducing the efficacy of radiotherapy [1,2,3]. Evaluation of the molecular mechanisms of radiotherapy resistance and identification of ways to increase the radiosensitivity of tumors are of great significance for improving the efficacy of tumor therapy. After X-ray exposure, tumor cells undergo DNA damage and activate programmed cell death and mitotic disruption pathways, eventually leading to death [4]. During DNA damage, epithelial-mesenchymal transition (EMT) of tumor cells during radiation promotes anti-radiation effects [5,6]. Tumor cells possess stem cell-like characteristics after EMT, leading to a certain resistance to radiotherapy [5,10]

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Results

Conclusion