Cargando…
MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN
Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and wh...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356677/ https://www.ncbi.nlm.nih.gov/pubmed/27811366 http://dx.doi.org/10.18632/oncotarget.13022 |
_version_ | 1782515889395990528 |
---|---|
author | Xue, Xinying Liu, Yuxia Wang, Yong Meng, Mingming Wang, Kaifei Zang, Xuefeng Zhao, Sheng Sun, Xiaohua Cui, Lei Pan, Lei Liu, Sanhong |
author_facet | Xue, Xinying Liu, Yuxia Wang, Yong Meng, Mingming Wang, Kaifei Zang, Xuefeng Zhao, Sheng Sun, Xiaohua Cui, Lei Pan, Lei Liu, Sanhong |
author_sort | Xue, Xinying |
collection | PubMed |
description | Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC. |
format | Online Article Text |
id | pubmed-5356677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53566772017-04-26 MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN Xue, Xinying Liu, Yuxia Wang, Yong Meng, Mingming Wang, Kaifei Zang, Xuefeng Zhao, Sheng Sun, Xiaohua Cui, Lei Pan, Lei Liu, Sanhong Oncotarget Research Paper Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC. Impact Journals LLC 2016-11-02 /pmc/articles/PMC5356677/ /pubmed/27811366 http://dx.doi.org/10.18632/oncotarget.13022 Text en Copyright: © 2016 Xue et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xue, Xinying Liu, Yuxia Wang, Yong Meng, Mingming Wang, Kaifei Zang, Xuefeng Zhao, Sheng Sun, Xiaohua Cui, Lei Pan, Lei Liu, Sanhong MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title | MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title_full | MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title_fullStr | MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title_full_unstemmed | MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title_short | MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN |
title_sort | mir-21 and mir-155 promote non-small cell lung cancer progression by downregulating socs1, socs6, and pten |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356677/ https://www.ncbi.nlm.nih.gov/pubmed/27811366 http://dx.doi.org/10.18632/oncotarget.13022 |
work_keys_str_mv | AT xuexinying mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT liuyuxia mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT wangyong mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT mengmingming mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT wangkaifei mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT zangxuefeng mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT zhaosheng mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT sunxiaohua mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT cuilei mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT panlei mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten AT liusanhong mir21andmir155promotenonsmallcelllungcancerprogressionbydownregulatingsocs1socs6andpten |