Cargando…
lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition
The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was con...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479258/ https://www.ncbi.nlm.nih.gov/pubmed/32882480 http://dx.doi.org/10.1016/j.omtn.2020.08.003 |
_version_ | 1783580233129000960 |
---|---|
author | Wang, Peng Chen, Weixiong Ma, Tongtong Lin, Zhaoyu Liu, Chongbin Liu, Youhua Hou, Fan Fan |
author_facet | Wang, Peng Chen, Weixiong Ma, Tongtong Lin, Zhaoyu Liu, Chongbin Liu, Youhua Hou, Fan Fan |
author_sort | Wang, Peng |
collection | PubMed |
description | The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-β/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-β/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-β receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs. |
format | Online Article Text |
id | pubmed-7479258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-74792582020-09-17 lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition Wang, Peng Chen, Weixiong Ma, Tongtong Lin, Zhaoyu Liu, Chongbin Liu, Youhua Hou, Fan Fan Mol Ther Nucleic Acids Original Article The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-β/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-β/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-β receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs. American Society of Gene & Cell Therapy 2020-08-05 /pmc/articles/PMC7479258/ /pubmed/32882480 http://dx.doi.org/10.1016/j.omtn.2020.08.003 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Wang, Peng Chen, Weixiong Ma, Tongtong Lin, Zhaoyu Liu, Chongbin Liu, Youhua Hou, Fan Fan lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title | lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title_full | lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title_fullStr | lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title_full_unstemmed | lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title_short | lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-β-Induced Epithelial-Mesenchymal Transition |
title_sort | lncrna lnc-tsi inhibits metastasis of clear cell renal cell carcinoma by suppressing tgf-β-induced epithelial-mesenchymal transition |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479258/ https://www.ncbi.nlm.nih.gov/pubmed/32882480 http://dx.doi.org/10.1016/j.omtn.2020.08.003 |
work_keys_str_mv | AT wangpeng lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT chenweixiong lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT matongtong lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT linzhaoyu lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT liuchongbin lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT liuyouhua lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition AT houfanfan lncrnalnctsiinhibitsmetastasisofclearcellrenalcellcarcinomabysuppressingtgfbinducedepithelialmesenchymaltransition |