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LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling

BACKGROUND: Thyroid cancer is one of the most prevalent malignancies in endocrine system. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. In the present study, we attempted to provide n...

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Detalles Bibliográficos
Autores principales: Liu, Hua, Deng, Haoyu, Zhao, Yajie, Li, Can, Liang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249781/
https://www.ncbi.nlm.nih.gov/pubmed/30463570
http://dx.doi.org/10.1186/s13046-018-0950-9
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author Liu, Hua
Deng, Haoyu
Zhao, Yajie
Li, Can
Liang, Yu
author_facet Liu, Hua
Deng, Haoyu
Zhao, Yajie
Li, Can
Liang, Yu
author_sort Liu, Hua
collection PubMed
description BACKGROUND: Thyroid cancer is one of the most prevalent malignancies in endocrine system. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. In the present study, we attempted to provide novel basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction. METHODS: The expression and cellular function of XIST (X-inactive specific transcript) was determined. miRNAs which may be direct targets of XIST were screened for from online GEO database and miR-34a was selected. Next, the predicted binding between XIST and miR-34a, and the dynamic effect of XIST and miR-34a on downstream MET (hepatocyte growth factor receptor)-PI3K (phosphoinositide 3-kinase)-AKT (α-serine/threonine-protein kinase) signaling was evaluated. RESULTS: XIST was significantly up-regulated in thyroid cancer tissues and cell lines; XIST knockdown suppressed the cell proliferation in vivo and the tumor growth in vitro. Based on online database and online tool prediction results, miR-34a was underexpressed in thyroid cancer and might be a direct target of XIST. Herein, we confirmed the negative interaction between XIST and miR-34a; moreover, XIST knockdown could reduce the protein levels of MET, a downstream target of miR-34a, and the phosphorylation of PI3K and AKT. In thyroid cancer tissues, MET mRNA and protein levels of MET were up-regulated; MET was positively correlated with XIST while negatively correlated with miR-34a, further confirming that XIST serves as a ceRNA for miR-34a through sponging miR-34a, competing with MET for miR-34a binding, and finally modulating thyroid cancer cell proliferation and tumor growth. CONCLUSION: In the present study, we provided novel experimental basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0950-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-62497812018-11-26 LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling Liu, Hua Deng, Haoyu Zhao, Yajie Li, Can Liang, Yu J Exp Clin Cancer Res Research BACKGROUND: Thyroid cancer is one of the most prevalent malignancies in endocrine system. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. In the present study, we attempted to provide novel basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction. METHODS: The expression and cellular function of XIST (X-inactive specific transcript) was determined. miRNAs which may be direct targets of XIST were screened for from online GEO database and miR-34a was selected. Next, the predicted binding between XIST and miR-34a, and the dynamic effect of XIST and miR-34a on downstream MET (hepatocyte growth factor receptor)-PI3K (phosphoinositide 3-kinase)-AKT (α-serine/threonine-protein kinase) signaling was evaluated. RESULTS: XIST was significantly up-regulated in thyroid cancer tissues and cell lines; XIST knockdown suppressed the cell proliferation in vivo and the tumor growth in vitro. Based on online database and online tool prediction results, miR-34a was underexpressed in thyroid cancer and might be a direct target of XIST. Herein, we confirmed the negative interaction between XIST and miR-34a; moreover, XIST knockdown could reduce the protein levels of MET, a downstream target of miR-34a, and the phosphorylation of PI3K and AKT. In thyroid cancer tissues, MET mRNA and protein levels of MET were up-regulated; MET was positively correlated with XIST while negatively correlated with miR-34a, further confirming that XIST serves as a ceRNA for miR-34a through sponging miR-34a, competing with MET for miR-34a binding, and finally modulating thyroid cancer cell proliferation and tumor growth. CONCLUSION: In the present study, we provided novel experimental basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0950-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-21 /pmc/articles/PMC6249781/ /pubmed/30463570 http://dx.doi.org/10.1186/s13046-018-0950-9 Text en © The Author(s). 2018 Open AccessThis 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liu, Hua
Deng, Haoyu
Zhao, Yajie
Li, Can
Liang, Yu
LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title_full LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title_fullStr LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title_full_unstemmed LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title_short LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling
title_sort lncrna xist/mir-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through met-pi3k-akt signaling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249781/
https://www.ncbi.nlm.nih.gov/pubmed/30463570
http://dx.doi.org/10.1186/s13046-018-0950-9
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