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LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis
Non‐small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigene...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724482/ https://www.ncbi.nlm.nih.gov/pubmed/33146951 http://dx.doi.org/10.1002/cam4.3570 |
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author | Wang, Dan Zhang, Suhong Zhao, Min Chen, Fengling |
author_facet | Wang, Dan Zhang, Suhong Zhao, Min Chen, Fengling |
author_sort | Wang, Dan |
collection | PubMed |
description | Non‐small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigenesis is blurry. This paper aims to investigate the theory of MALAT1 action in NSCLC progression. The levels of MALAT1, microRNA (miR)‐185‐5p, and mouse double minute 4 protein (MDM4) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot. Cell proliferation and apoptosis were, respectively, determined by 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay, and flow cytometry. Cell migratory and invasive abilities were inspected by transwell assay. The binding relationship between miR‐185‐5p and MALAT1 or MDM4 was confirmed by dual‐luciferase reporter assay. The impacts of MALAT1 on tumor growth in vivo were measured by a xenograft experiment. We found MALAT1 and MDM4 were upregulated and MALAT1 positively regulated the MDM4 expression. MALAT1 and MDM4 deletion significantly hindered the proliferation, metastasis, and expedited the apoptosis of NSCLC cells. MDM4 overexpression partly overturned the influence of MALAT1 downregulation on cell development. Moreover, miR‐185‐5p, as a target of MALAT1, could directly target MDM4, and miR‐185‐5p upregulation exerted inhibitory effects on NSCLC cells. Besides, knockdown of MALAT1 inhibited tumor growth in vivo through miR‐185‐5p/MDM4 axis in NSCLC. Collectively, MALAT1 contributed to proliferation, migration, invasion, and impeded apoptosis by regulating the MDM4 expression mediated by miR‐185‐5p in NSCLC cells. |
format | Online Article Text |
id | pubmed-7724482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77244822020-12-13 LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis Wang, Dan Zhang, Suhong Zhao, Min Chen, Fengling Cancer Med Cancer Biology Non‐small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigenesis is blurry. This paper aims to investigate the theory of MALAT1 action in NSCLC progression. The levels of MALAT1, microRNA (miR)‐185‐5p, and mouse double minute 4 protein (MDM4) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot. Cell proliferation and apoptosis were, respectively, determined by 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay, and flow cytometry. Cell migratory and invasive abilities were inspected by transwell assay. The binding relationship between miR‐185‐5p and MALAT1 or MDM4 was confirmed by dual‐luciferase reporter assay. The impacts of MALAT1 on tumor growth in vivo were measured by a xenograft experiment. We found MALAT1 and MDM4 were upregulated and MALAT1 positively regulated the MDM4 expression. MALAT1 and MDM4 deletion significantly hindered the proliferation, metastasis, and expedited the apoptosis of NSCLC cells. MDM4 overexpression partly overturned the influence of MALAT1 downregulation on cell development. Moreover, miR‐185‐5p, as a target of MALAT1, could directly target MDM4, and miR‐185‐5p upregulation exerted inhibitory effects on NSCLC cells. Besides, knockdown of MALAT1 inhibited tumor growth in vivo through miR‐185‐5p/MDM4 axis in NSCLC. Collectively, MALAT1 contributed to proliferation, migration, invasion, and impeded apoptosis by regulating the MDM4 expression mediated by miR‐185‐5p in NSCLC cells. John Wiley and Sons Inc. 2020-11-04 /pmc/articles/PMC7724482/ /pubmed/33146951 http://dx.doi.org/10.1002/cam4.3570 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Wang, Dan Zhang, Suhong Zhao, Min Chen, Fengling LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title_full | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title_fullStr | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title_full_unstemmed | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title_short | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis |
title_sort | lncrna malat1 accelerates non‐small cell lung cancer progression via regulating mir‐185‐5p/mdm4 axis |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724482/ https://www.ncbi.nlm.nih.gov/pubmed/33146951 http://dx.doi.org/10.1002/cam4.3570 |
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