Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and...

Full description

Bibliographic Details
Main Authors: Shu-Feng Xu, Yue Zheng, Ling Zhang, Ping Wang, Chun-Mi Niu, Tong Wu, Qi Tian, Xiao-Bo Yin, Shan-Shan Shi, Lei Zheng, Li-Ming Gao
Format: Article
Language:English
Published: Elsevier 2019-12-01
Series:Molecular Therapy: Nucleic Acids
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253119302173
id doaj-36d3179bd7574930bb2c181e8d17857a
record_format Article
spelling doaj-36d3179bd7574930bb2c181e8d17857a2020-11-25T01:31:36ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-12-0118166182Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung AdenocarcinomaShu-Feng Xu0Yue Zheng1Ling Zhang2Ping Wang3Chun-Mi Niu4Tong Wu5Qi Tian6Xiao-Bo Yin7Shan-Shan Shi8Lei Zheng9Li-Ming Gao10Department of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaDepartment of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaDepartment of Respiratory, Hebei Chest Hospital, Shijiazhuang 050021, P.R. ChinaDepartment of Respiratory, Chinese PLA General Hospital, Beijing 100853, P.R. ChinaDepartment of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaMedical Students, Hebei Medical University, Shijiazhuang 050017, P.R. ChinaDepartment of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaDepartment of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaMedical Students, Hebei Medical University, Shijiazhuang 050017, P.R. ChinaDepartment of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. ChinaDepartment of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. China; Corresponding author: Li-Ming Gao, Department of Oncology, The First Hospital of Qinhuangdao, No. 258, Wenhua Road, Haigang District, Qinhuangdao 066000, Hebei Province, P.R. China.Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR. Keywords: lung adenocarcinoma, long non-coding RNA LINC00628, LAMA3, methylation, migration, invasion, vincristine, drug resistancehttp://www.sciencedirect.com/science/article/pii/S2162253119302173
collection DOAJ
language English
format Article
sources DOAJ
author Shu-Feng Xu
Yue Zheng
Ling Zhang
Ping Wang
Chun-Mi Niu
Tong Wu
Qi Tian
Xiao-Bo Yin
Shan-Shan Shi
Lei Zheng
Li-Ming Gao
spellingShingle Shu-Feng Xu
Yue Zheng
Ling Zhang
Ping Wang
Chun-Mi Niu
Tong Wu
Qi Tian
Xiao-Bo Yin
Shan-Shan Shi
Lei Zheng
Li-Ming Gao
Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
Molecular Therapy: Nucleic Acids
author_facet Shu-Feng Xu
Yue Zheng
Ling Zhang
Ping Wang
Chun-Mi Niu
Tong Wu
Qi Tian
Xiao-Bo Yin
Shan-Shan Shi
Lei Zheng
Li-Ming Gao
author_sort Shu-Feng Xu
title Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
title_short Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
title_full Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
title_fullStr Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
title_full_unstemmed Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma
title_sort long non-coding rna linc00628 interacts epigenetically with the lama3 promoter and contributes to lung adenocarcinoma
publisher Elsevier
series Molecular Therapy: Nucleic Acids
issn 2162-2531
publishDate 2019-12-01
description Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR. Keywords: lung adenocarcinoma, long non-coding RNA LINC00628, LAMA3, methylation, migration, invasion, vincristine, drug resistance
url http://www.sciencedirect.com/science/article/pii/S2162253119302173
work_keys_str_mv AT shufengxu longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT yuezheng longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT lingzhang longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT pingwang longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT chunminiu longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT tongwu longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT qitian longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT xiaoboyin longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT shanshanshi longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT leizheng longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
AT liminggao longnoncodingrnalinc00628interactsepigeneticallywiththelama3promoterandcontributestolungadenocarcinoma
_version_ 1725085717678260224