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MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis

Megakaryocytic leukemia 1 (MKL1) is a key transcription factor involved in non-small cell lung cancer (NSCLC) growth and metastasis. Yet, its downstream target genes, especially long non-coding RNA (lncRNA) targets, are poorly investigated. In this study, we employed lncRNA array technology to ident...

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Autores principales: Fan, Huijie, Yuan, Jing, Li, Yaqing, Jia, Yongxu, Li, Jing, Wang, Xiaofeng, Li, Xingya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838315/
https://www.ncbi.nlm.nih.gov/pubmed/33500406
http://dx.doi.org/10.1038/s41419-021-03399-z
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author Fan, Huijie
Yuan, Jing
Li, Yaqing
Jia, Yongxu
Li, Jing
Wang, Xiaofeng
Li, Xingya
author_facet Fan, Huijie
Yuan, Jing
Li, Yaqing
Jia, Yongxu
Li, Jing
Wang, Xiaofeng
Li, Xingya
author_sort Fan, Huijie
collection PubMed
description Megakaryocytic leukemia 1 (MKL1) is a key transcription factor involved in non-small cell lung cancer (NSCLC) growth and metastasis. Yet, its downstream target genes, especially long non-coding RNA (lncRNA) targets, are poorly investigated. In this study, we employed lncRNA array technology to identify differentially expressed lncRNAs in NSCLC cells with or without overexpression of MKL1. Candidate lncRNAs were further explored for their clinical significance and function in NSCLC. The results showed that MKL1 promoted the expression of lncRNA SNHG18 in NSCLC cells. SNHG18 upregulation in NSCLC specimens correlated with lymph node metastasis and reduced overall survival of NSCLC patients. SNHG18 expression served as an independent prognostic factor for NSCLC. Knockdown of SNHG18 blocked MKL1-induced growth and invasion of NSCLC cells in vitro. Animal studies validated the requirement for SNHG18 in NSCLC growth and metastasis. Moreover, overexpression of SNHG18 promoted NSCLC cell proliferation and invasion. Mechanically, SNHG18 exerted its prometastatic effects on NSCLC cells through repression of miR-211-5p and induction of BRD4. Clinical evidence indicated that SNHG18 expression was negatively correlated with miR-211-5p expression in NSCLC tissues. Altogether, SNHG18 acts as a lncRNA mediator of MKL1 in NSCLC. SNHG18 facilitates NSCLC growth and metastasis by modulating the miR-211-5p/BRD4 axis. Therefore, SNHG18 may be a potential therapeutic target for the treatment of NSCLC.
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spelling pubmed-78383152021-01-29 MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis Fan, Huijie Yuan, Jing Li, Yaqing Jia, Yongxu Li, Jing Wang, Xiaofeng Li, Xingya Cell Death Dis Article Megakaryocytic leukemia 1 (MKL1) is a key transcription factor involved in non-small cell lung cancer (NSCLC) growth and metastasis. Yet, its downstream target genes, especially long non-coding RNA (lncRNA) targets, are poorly investigated. In this study, we employed lncRNA array technology to identify differentially expressed lncRNAs in NSCLC cells with or without overexpression of MKL1. Candidate lncRNAs were further explored for their clinical significance and function in NSCLC. The results showed that MKL1 promoted the expression of lncRNA SNHG18 in NSCLC cells. SNHG18 upregulation in NSCLC specimens correlated with lymph node metastasis and reduced overall survival of NSCLC patients. SNHG18 expression served as an independent prognostic factor for NSCLC. Knockdown of SNHG18 blocked MKL1-induced growth and invasion of NSCLC cells in vitro. Animal studies validated the requirement for SNHG18 in NSCLC growth and metastasis. Moreover, overexpression of SNHG18 promoted NSCLC cell proliferation and invasion. Mechanically, SNHG18 exerted its prometastatic effects on NSCLC cells through repression of miR-211-5p and induction of BRD4. Clinical evidence indicated that SNHG18 expression was negatively correlated with miR-211-5p expression in NSCLC tissues. Altogether, SNHG18 acts as a lncRNA mediator of MKL1 in NSCLC. SNHG18 facilitates NSCLC growth and metastasis by modulating the miR-211-5p/BRD4 axis. Therefore, SNHG18 may be a potential therapeutic target for the treatment of NSCLC. Nature Publishing Group UK 2021-01-26 /pmc/articles/PMC7838315/ /pubmed/33500406 http://dx.doi.org/10.1038/s41419-021-03399-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fan, Huijie
Yuan, Jing
Li, Yaqing
Jia, Yongxu
Li, Jing
Wang, Xiaofeng
Li, Xingya
MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title_full MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title_fullStr MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title_full_unstemmed MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title_short MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
title_sort mkl1-induced lncrna snhg18 drives the growth and metastasis of non-small cell lung cancer via the mir-211-5p/brd4 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838315/
https://www.ncbi.nlm.nih.gov/pubmed/33500406
http://dx.doi.org/10.1038/s41419-021-03399-z
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