Cargando…

TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling

ABSTRACT: The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Zhiliang, Chen, Zhaoli, Li, Yuan, Wang, Jingnan, Zhang, Zhirong, Che, Yun, Huang, Jianbing, Sun, Shouguo, Mao, Shuangshuang, Lei, Yuanyuan, Gao, Yibo, He, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859688/
https://www.ncbi.nlm.nih.gov/pubmed/29379981
http://dx.doi.org/10.1007/s00109-018-1621-1
_version_ 1783307873287143424
author Lu, Zhiliang
Chen, Zhaoli
Li, Yuan
Wang, Jingnan
Zhang, Zhirong
Che, Yun
Huang, Jianbing
Sun, Shouguo
Mao, Shuangshuang
Lei, Yuanyuan
Gao, Yibo
He, Jie
author_facet Lu, Zhiliang
Chen, Zhaoli
Li, Yuan
Wang, Jingnan
Zhang, Zhirong
Che, Yun
Huang, Jianbing
Sun, Shouguo
Mao, Shuangshuang
Lei, Yuanyuan
Gao, Yibo
He, Jie
author_sort Lu, Zhiliang
collection PubMed
description ABSTRACT: The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in vivo, and mechanism studies showed that NKILA repressed MMP14 expression by inhibiting IκBα phosphorylation and NF-κB activation. Collectively, these findings suggest that the TGF-β-induced lncRNA NKILA has potential as an antimetastasis therapy. KEY MESSAGES: Long noncoding RNA NKILA could be remarkably upregulated by classical TGF-β signal pathway in ESCC. NKILA was significantly downregulated in esophageal squamous cell carcinoma and negatively correlated with TNM stage. NKILA inhibits ESCC cell metastasis via repressing MMP14 expression by suppressing the phosphorylation of IκBα and NF-κB activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-018-1621-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5859688
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-58596882018-03-22 TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling Lu, Zhiliang Chen, Zhaoli Li, Yuan Wang, Jingnan Zhang, Zhirong Che, Yun Huang, Jianbing Sun, Shouguo Mao, Shuangshuang Lei, Yuanyuan Gao, Yibo He, Jie J Mol Med (Berl) Original Article ABSTRACT: The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in vivo, and mechanism studies showed that NKILA repressed MMP14 expression by inhibiting IκBα phosphorylation and NF-κB activation. Collectively, these findings suggest that the TGF-β-induced lncRNA NKILA has potential as an antimetastasis therapy. KEY MESSAGES: Long noncoding RNA NKILA could be remarkably upregulated by classical TGF-β signal pathway in ESCC. NKILA was significantly downregulated in esophageal squamous cell carcinoma and negatively correlated with TNM stage. NKILA inhibits ESCC cell metastasis via repressing MMP14 expression by suppressing the phosphorylation of IκBα and NF-κB activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-018-1621-1) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-01-29 2018 /pmc/articles/PMC5859688/ /pubmed/29379981 http://dx.doi.org/10.1007/s00109-018-1621-1 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Original Article
Lu, Zhiliang
Chen, Zhaoli
Li, Yuan
Wang, Jingnan
Zhang, Zhirong
Che, Yun
Huang, Jianbing
Sun, Shouguo
Mao, Shuangshuang
Lei, Yuanyuan
Gao, Yibo
He, Jie
TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title_full TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title_fullStr TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title_full_unstemmed TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title_short TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling
title_sort tgf-β-induced nkila inhibits escc cell migration and invasion through nf-κb/mmp14 signaling
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859688/
https://www.ncbi.nlm.nih.gov/pubmed/29379981
http://dx.doi.org/10.1007/s00109-018-1621-1
work_keys_str_mv AT luzhiliang tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT chenzhaoli tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT liyuan tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT wangjingnan tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT zhangzhirong tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT cheyun tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT huangjianbing tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT sunshouguo tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT maoshuangshuang tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT leiyuanyuan tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT gaoyibo tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling
AT hejie tgfbinducednkilainhibitsescccellmigrationandinvasionthroughnfkbmmp14signaling