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The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2

High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based...

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Autores principales: Wang, Yuan, Chen, Fuquan, Yang, Zhe, Zhao, Man, Zhang, Shuqin, Gao, Yuen, Feng, Jinyan, Yang, Guang, Zhang, Weiying, Ye, Lihong, Zhang, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437003/
https://www.ncbi.nlm.nih.gov/pubmed/28522832
http://dx.doi.org/10.1038/s41598-017-02311-0
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author Wang, Yuan
Chen, Fuquan
Yang, Zhe
Zhao, Man
Zhang, Shuqin
Gao, Yuen
Feng, Jinyan
Yang, Guang
Zhang, Weiying
Ye, Lihong
Zhang, Xiaodong
author_facet Wang, Yuan
Chen, Fuquan
Yang, Zhe
Zhao, Man
Zhang, Shuqin
Gao, Yuen
Feng, Jinyan
Yang, Guang
Zhang, Weiying
Ye, Lihong
Zhang, Xiaodong
author_sort Wang, Yuan
collection PubMed
description High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3′-untranslated region (3′UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3′UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells. Then, Dicer contributes to the generation of the fragment HMGA2-sh-3p20 from the HMGA2-sh. HMGA2-sh-3p20 was screened by PCR analysis. Interestingly, HMGA2-sh-3p20 increased the expression of HMGA2 through antagonizing the tristetraprolin (TTP)-mediated degradation of HMGA2. HMGA2-sh-3p20 inhibited the expression of PTEN by targeting the 3′UTR of PTEN mRNA. In addition, the overexpression of PTEN could downregulate HMGA2 expression. Significantly, we documented the ability of HMGA2-sh-3p20 to promote the growth of hepatoma cells in vitro and in vivo. Thus, we conclude that the fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR promotes the growth of hepatoma cells by upregulating HMGA2. Our finding provides new insights into the mechanism by which HMGA2 enhances hepatocarcinogenesis.
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spelling pubmed-54370032017-05-19 The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2 Wang, Yuan Chen, Fuquan Yang, Zhe Zhao, Man Zhang, Shuqin Gao, Yuen Feng, Jinyan Yang, Guang Zhang, Weiying Ye, Lihong Zhang, Xiaodong Sci Rep Article High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3′-untranslated region (3′UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3′UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells. Then, Dicer contributes to the generation of the fragment HMGA2-sh-3p20 from the HMGA2-sh. HMGA2-sh-3p20 was screened by PCR analysis. Interestingly, HMGA2-sh-3p20 increased the expression of HMGA2 through antagonizing the tristetraprolin (TTP)-mediated degradation of HMGA2. HMGA2-sh-3p20 inhibited the expression of PTEN by targeting the 3′UTR of PTEN mRNA. In addition, the overexpression of PTEN could downregulate HMGA2 expression. Significantly, we documented the ability of HMGA2-sh-3p20 to promote the growth of hepatoma cells in vitro and in vivo. Thus, we conclude that the fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR promotes the growth of hepatoma cells by upregulating HMGA2. Our finding provides new insights into the mechanism by which HMGA2 enhances hepatocarcinogenesis. Nature Publishing Group UK 2017-05-18 /pmc/articles/PMC5437003/ /pubmed/28522832 http://dx.doi.org/10.1038/s41598-017-02311-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Yuan
Chen, Fuquan
Yang, Zhe
Zhao, Man
Zhang, Shuqin
Gao, Yuen
Feng, Jinyan
Yang, Guang
Zhang, Weiying
Ye, Lihong
Zhang, Xiaodong
The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title_full The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title_fullStr The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title_full_unstemmed The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title_short The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3′UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2
title_sort fragment hmga2-sh-3p20 from hmga2 mrna 3′utr promotes the growth of hepatoma cells by upregulating hmga2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437003/
https://www.ncbi.nlm.nih.gov/pubmed/28522832
http://dx.doi.org/10.1038/s41598-017-02311-0
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