Downregulation of histone‑lysine N‑methyltransferase EZH2 inhibits cell viability and enhances chemosensitivity in lung cancer cells

Cao,Ziyang; Wu,Wei; Wei,Haiting; Zhang,Wei; Huang,Yan; Dong,Zhengwei

doi:10.3892/ol.2020.12287

Downregulation of histone‑lysine N‑methyltransferase EZH2 inhibits cell viability and enhances chemosensitivity in lung cancer cells

Authors:
- Ziyang Cao
- Wei Wu
- Haiting Wei
- Wei Zhang
- Yan Huang
- Zhengwei Dong
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Affiliations: Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, P.R. China
Published online on: November 11, 2020 https://doi.org/10.3892/ol.2020.12287
Article Number: 26
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histone‑lysine N‑methyltransferase EZH2 (EZH2) is the principle component of the polycomb repressive complex 2 (PRC2)/embryonic ectoderm development protein‑EZH2 complex, which promotes tumorigenesis by repressing transcription of tumor suppressor genes. EZH2 is considered a key marker in several types of cancer, such as colorectal and prostate cancer. However, the molecular mechanisms and clinical value of EZH2 in lung cancer have not yet been fully investigated. The aim of the present study was to investigate the functions of EZH2 in lung cancer progression and to determine whether treatment with an EZH2 inhibitor enhanced the chemosensitivity of lung cancer cells to cisplatin (CDDP). At the logarithmic growth phase, A549 cells were treated with a small interfering (si)RNA‑EZH2, and cell viability was detected using an MTT assay. The degree of apoptosis and cell cycle were detected using flow cytometry. Cell migration and invasion were detected via wound healing and Transwell Matrigel assays. According to information from the Gene Expression Omnibus database, the results of the present study demonstrated that EZH2 was upregulated in lung cancer. Furthermore, overexpression of EZH2 was associated with poor patient prognosis, while EZH2 knockdown inhibited cell viability and migration, and enhanced apoptosis and chemosensitivity in a lung cancer cell line. EZH2 knockdown and treatment of A549 cells using EZH2 inhibitor elevated the inhibitory effects of CDDP on cell viability and apoptosis. Western blot and reverse transcription‑quantitative PCR analyses were performed to assess the expression levels of relative protein and mRNA, respectively, in A549 cells treated with siRNA‑EZH2 or with CDDP. Overall, the results of the present study demonstrated that high EZH2 expression was associated with poor prognosis, accompanied with a potential impairment of migration and viability in lung cancer cells. These findings suggest that EZH2 may act as a candidate molecular target for gene therapy, and treatment with EZH2 inhibitor may be used to increase chemosensitivity to CDDP agents in lung cancer.

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