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Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer

Metastasis is the primary reason of death in patients with cancer. Small nucleolar noncoding RNAs (snoRNAs) are conserved 60–300 nucleotide noncoding RNAs, involved in post‐transcriptional regulation of mRNAs and noncoding RNAs. Despite their essential roles in cancer, the roles of snoRNAs in epithe...

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Autores principales: Hu, Ting, Lu, Chong, Xia, Yun, Wu, Lu, Song, Junlong, Chen, Chuang, Wang, Qiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067147/
https://www.ncbi.nlm.nih.gov/pubmed/35100495
http://dx.doi.org/10.1002/1878-0261.13186
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author Hu, Ting
Lu, Chong
Xia, Yun
Wu, Lu
Song, Junlong
Chen, Chuang
Wang, Qiong
author_facet Hu, Ting
Lu, Chong
Xia, Yun
Wu, Lu
Song, Junlong
Chen, Chuang
Wang, Qiong
author_sort Hu, Ting
collection PubMed
description Metastasis is the primary reason of death in patients with cancer. Small nucleolar noncoding RNAs (snoRNAs) are conserved 60–300 nucleotide noncoding RNAs, involved in post‐transcriptional regulation of mRNAs and noncoding RNAs. Despite their essential roles in cancer, the roles of snoRNAs in epithelial‐mesenchymal transition (EMT)‐induced metastasis have not been studied extensively. Here, we used small RNA sequencing to screen for snoRNAs related to EMT and breast cancer metastasis. We found a higher expression of SNORA71A in metastatic breast cancer tissues compared to nonmetastatic samples. Additionally, SNORA71A promoted the proliferation, migration, invasion and EMT of MCF‐7 and MDA‐MB‐231 cells. Mechanistically, SNORA71A elevated mRNA and protein levels of ROCK2, a negative regulator of TGF‐β signaling. Rescue assays showed ROCK2 abrogated the SNORA71A‐mediated increase in proliferation, migration, invasion and EMT. Binding of SNORA71A to mRNA stability regulatory protein G3BP1, increased ROCK2 mRNA half‐life. Furthermore, G3BP1 depletion abolished the SNORA71A‐mediated upregulation of ROCK2. In vivo, SNORA71A overexpression promoted breast tumor growth, and SNORA71A knockdown inhibited breast cancer growth and metastasis. We suggest SNORA71A enhances metastasis of breast cancer by binding to G3BP1 and stabilizing ROCK2.
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spelling pubmed-90671472022-05-09 Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer Hu, Ting Lu, Chong Xia, Yun Wu, Lu Song, Junlong Chen, Chuang Wang, Qiong Mol Oncol Research Articles Metastasis is the primary reason of death in patients with cancer. Small nucleolar noncoding RNAs (snoRNAs) are conserved 60–300 nucleotide noncoding RNAs, involved in post‐transcriptional regulation of mRNAs and noncoding RNAs. Despite their essential roles in cancer, the roles of snoRNAs in epithelial‐mesenchymal transition (EMT)‐induced metastasis have not been studied extensively. Here, we used small RNA sequencing to screen for snoRNAs related to EMT and breast cancer metastasis. We found a higher expression of SNORA71A in metastatic breast cancer tissues compared to nonmetastatic samples. Additionally, SNORA71A promoted the proliferation, migration, invasion and EMT of MCF‐7 and MDA‐MB‐231 cells. Mechanistically, SNORA71A elevated mRNA and protein levels of ROCK2, a negative regulator of TGF‐β signaling. Rescue assays showed ROCK2 abrogated the SNORA71A‐mediated increase in proliferation, migration, invasion and EMT. Binding of SNORA71A to mRNA stability regulatory protein G3BP1, increased ROCK2 mRNA half‐life. Furthermore, G3BP1 depletion abolished the SNORA71A‐mediated upregulation of ROCK2. In vivo, SNORA71A overexpression promoted breast tumor growth, and SNORA71A knockdown inhibited breast cancer growth and metastasis. We suggest SNORA71A enhances metastasis of breast cancer by binding to G3BP1 and stabilizing ROCK2. John Wiley and Sons Inc. 2022-03-30 2022-05 /pmc/articles/PMC9067147/ /pubmed/35100495 http://dx.doi.org/10.1002/1878-0261.13186 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hu, Ting
Lu, Chong
Xia, Yun
Wu, Lu
Song, Junlong
Chen, Chuang
Wang, Qiong
Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title_full Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title_fullStr Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title_full_unstemmed Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title_short Small nucleolar RNA SNORA71A promotes epithelial‐mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer
title_sort small nucleolar rna snora71a promotes epithelial‐mesenchymal transition by maintaining rock2 mrna stability in breast cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067147/
https://www.ncbi.nlm.nih.gov/pubmed/35100495
http://dx.doi.org/10.1002/1878-0261.13186
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