Inhibition of DNA methyltransferase 1 by RNA interference reverses epithelial‑mesenchymal transition in highly metastatic 95D lung cancer cells by inhibiting the Wnt signaling pathway

Bu,Xiancong; Zhang,Xiangyan; Xu,Jinhong; Yang,Heping; Zhou,Xiangdong; Wang,Haijing; Gong,Liang

doi:10.3892/ol.2018.8449

Inhibition of DNA methyltransferase 1 by RNA interference reverses epithelial‑mesenchymal transition in highly metastatic 95D lung cancer cells by inhibiting the Wnt signaling pathway

Authors:
- Xiancong Bu
- Xiangyan Zhang
- Jinhong Xu
- Heping Yang
- Xiangdong Zhou
- Haijing Wang
- Liang Gong
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Affiliations: Department of Respiratory Medicine, Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, Shandong 276800, P.R. China, Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Institute for Tuberculosis Control and Prevention, Guizhou Provincial Center for Disease Control and Prevention, Guiyang, Guizhou 550004, P.R. China, Department of Respiratory Medicine, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China
Published online on: April 10, 2018 https://doi.org/10.3892/ol.2018.8449
Pages: 9242-9250
Copyright: © Bu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epigenetic modifications serve important roles in non‑small cell lung cancer (NSCLC) tumorigenesis; however, the role of DNA methyltransferase 1 (DNMT1) in lung cancer progression remains unclear. In the present study, the expression of DNMT1 in the human NSCLC cell lines 95D (high invasive ability) and 95C (low invasive ability) was analyzed by western blotting. The results demonstrated that the expression of DNMT1 in 95D cells was significantly higher, compared with in 95C cells and small airway epithelial cells. To further define the role of DNMT1 in tumor migration and invasion in NSCLC cells, RNA interference was used to silence DNMT1 expression. Depletion of DNMT1 significantly inhibited 95D cell invasion and migration. In addition, treatment with DNMT1 small interfering RNA resulted in compact cell morphology and significantly increased epithelial marker E‑cadherin expression whilst also decreasing the expression of certain mesenchymal markers, including vimentin and fibronectin. Suppression of DNMT1 increased cytoplasmic β‑catenin levels while downregulating nuclear β‑catenin and Snail, an important regulator of EMT. The results from the present study suggest that the inhibition of DNMT1 reverses the epithelial‑mesenchymal transition partly via the inhibition of the Wnt/β‑catenin signaling pathway, and therefore inhibits cell migration and invasion. These results indicate that targeting DNMT1 may inhibit tumor metastasis and that DNMT1 is a promising target for the novel treatment of lung cancer.

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