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Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological rol...

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Autores principales: Zhang, Juan, Fu, Jun, Pan, Yuliang, Zhang, Xi, Shen, Liangfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138046/
https://www.ncbi.nlm.nih.gov/pubmed/27942223
http://dx.doi.org/10.2147/OTT.S111291
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author Zhang, Juan
Fu, Jun
Pan, Yuliang
Zhang, Xi
Shen, Liangfang
author_facet Zhang, Juan
Fu, Jun
Pan, Yuliang
Zhang, Xi
Shen, Liangfang
author_sort Zhang, Juan
collection PubMed
description MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological role in non-small-cell lung cancer (NSCLC) is unknown. This study found that the expression of miR-1247 was significantly reduced in NSCLC cell lines and tumor tissues compared with matched normal lung tissues and cell lines as a result of DNA hypermethylation. Overexpression of miR-1247 or demethylation by 5-azacytidine (5-Aza) treatment dramatically inhibited cell growth, migration, invasion, and cell cycle progression. Furthermore, Stathmin 1 (STMN1) was found to be an immediate and functional target of miR-1247. The expression of STMN1 was significantly increased in NSCLC cell lines but was decreased by 5-Aza treatment. In addition, miR-1247 upregulation partially inhibited STMN1-induced promotion of migration and invasion of A549 and H1299 cells. The results suggest that miR-1247 was silenced by DNA methylation. MiR-1247 and its downstream target gene STMN1 may therefore be a future target for the treatment of NSCLC.
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spelling pubmed-51380462016-12-09 Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1 Zhang, Juan Fu, Jun Pan, Yuliang Zhang, Xi Shen, Liangfang Onco Targets Ther Original Research MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological role in non-small-cell lung cancer (NSCLC) is unknown. This study found that the expression of miR-1247 was significantly reduced in NSCLC cell lines and tumor tissues compared with matched normal lung tissues and cell lines as a result of DNA hypermethylation. Overexpression of miR-1247 or demethylation by 5-azacytidine (5-Aza) treatment dramatically inhibited cell growth, migration, invasion, and cell cycle progression. Furthermore, Stathmin 1 (STMN1) was found to be an immediate and functional target of miR-1247. The expression of STMN1 was significantly increased in NSCLC cell lines but was decreased by 5-Aza treatment. In addition, miR-1247 upregulation partially inhibited STMN1-induced promotion of migration and invasion of A549 and H1299 cells. The results suggest that miR-1247 was silenced by DNA methylation. MiR-1247 and its downstream target gene STMN1 may therefore be a future target for the treatment of NSCLC. Dove Medical Press 2016-12-01 /pmc/articles/PMC5138046/ /pubmed/27942223 http://dx.doi.org/10.2147/OTT.S111291 Text en © 2016 Zhang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhang, Juan
Fu, Jun
Pan, Yuliang
Zhang, Xi
Shen, Liangfang
Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title_full Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title_fullStr Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title_full_unstemmed Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title_short Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1
title_sort silencing of mir-1247 by dna methylation promoted non-small-cell lung cancer cell invasion and migration by effects of stmn1
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138046/
https://www.ncbi.nlm.nih.gov/pubmed/27942223
http://dx.doi.org/10.2147/OTT.S111291
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