Long non-coding RNA H19 is responsible for the progression of lung adenocarcinoma by mediating methylation-dependent repression of CDH1 promoter.

Abstract

Lung adenocarcinoma is a common histologic type of lung cancer with a high death rate globally. Increasing evidence shows that long non-coding RNA H19 (lncRNA H19) and CDH1 methylation are involved in multiple tumours. Here, we tried to investigate whether lncRNA H19 or CDH1 methylation could affect the development of lung adenocarcinoma. First, lung adenocarcinoma tissues were collected to detect CDH1 methylation. Then, the regulatory mechanisms of lncRNA H19 were detected mainly in concert with the treatment of overexpression of lncRNA H19, siRNA against lncRNA H19, overexpression of CDH1 and demethylating agent A-5az in lung adenocarcinoma A549 cell. The expression of lncRNA H19 and epithelial-mesenchymal transition (EMT)-related factors as well as cell proliferation, sphere-forming ability, apoptosis, migration and invasion were detected. Finally, we observed xenograft tumour in nude mice so as to ascertain tumorigenicity of lung adenocarcinoma cells. LncRNA H19 and methylation of CDH1 were highly expressed in lung adenocarcinoma tissues. A549 cells with silencing of lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation by demethylating agent 5-Az had suppressed cell proliferation, sphere-forming ability, apoptosis, migration and invasion, in addition to inhibited EMT process. Silencing lncRNA H19 could reduce methylation level of CDH1. In vivo, A549 cells with silencing lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation exhibited low tumorigenicity, reflected by the smaller tumour size and lighter tumour weight. Taken together, this study demonstrates that silencing of lncRNA H19 inhibits EMT and proliferation while promoting apoptosis of lung adenocarcinoma cells by inhibiting methylation of CDH1 promoter.

• Authors: Li-Ming Gao, Shu-Feng Xu, Yue Zheng, Ping Wang, Ling Zhang, Shan-Shan Shi, Tong Wu, Yang Li, Jing Zhao, Qi Tian, Xiao-Bo Yin, Lei Zheng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 9 Pg. 6411-6428 (09 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 31317666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Antigens, CD
• CDH1 protein, human
• Cadherins
• H19 long non-coding RNA
• RNA, Long Noncoding
• RNA, Small Interfering

Topics

• A549 Cells
• Adenocarcinoma of Lung (genetics)
• Adult
• Aged
• Animals
• Antigens, CD (genetics)
• Apoptosis (genetics)
• Cadherins (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Lung Neoplasms (genetics)
• Male
• Methylation
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Promoter Regions, Genetic (genetics)
• RNA, Long Noncoding (genetics)
• RNA, Small Interfering (genetics)
• Young Adult