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...
Main Authors: | , , , , , , , , , , |
---|---|
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 |