Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma.
<h4>Background & aims</h4>Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of hepatocellular carcinoma (HCC) was accompanied by a significant reductio...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089446&type=printable |
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| author | Tzu-Min Hung Cheng-Maw Ho Yen-Chun Liu Jia-Ling Lee Yow-Rong Liao Yao-Ming Wu Ming-Chih Ho Chien-Hung Chen Hong-Shiee Lai Po-Huang Lee |
| author_facet | Tzu-Min Hung Cheng-Maw Ho Yen-Chun Liu Jia-Ling Lee Yow-Rong Liao Yao-Ming Wu Ming-Chih Ho Chien-Hung Chen Hong-Shiee Lai Po-Huang Lee |
| author_sort | Tzu-Min Hung |
| collection | DOAJ |
| description | <h4>Background & aims</h4>Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of hepatocellular carcinoma (HCC) was accompanied by a significant reduction in serum IGF-1 levels. Here, we hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1 expression post-transcriptionally.<h4>Methods</h4>The miRNAs expression profiles in a dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA (miR)-190b, which was significantly up-regulated in HCC tumor tissues when compared with paired non-tumor tissues, was among those predicted to interact with 3'-untranslated region (UTR) of IGF-1. In order to explore the regulatory effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative real-time PCR, western blotting and immunofluorecence analysis were performed in HCC cells.<h4>Results</h4>Overexpression of miR-190b in Huh7 cells attenuated the expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and functional target of miR-190b. Additionally, low serum IGF-1 level was associated with insulin resistance and poor overall survival in HCC patients.<h4>Conclusions</h4>Increased expression of miR-190 may cause decreased IGF-1 in HCC development. Insulin resistance appears to be a part of the physiopathologic significance of decreased IGF-1 levels in HCC progression. This study provides a novel miRNA-mediated regulatory mechanism for controlling IGF-1 expression in HCC and elucidates the biological relevance of this interaction in HCC. |
| format | Article |
| id | doaj-art-96362b91c8424f01bd011c2df543d7cc |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-96362b91c8424f01bd011c2df543d7cc2025-08-20T02:15:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8944610.1371/journal.pone.0089446Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma.Tzu-Min HungCheng-Maw HoYen-Chun LiuJia-Ling LeeYow-Rong LiaoYao-Ming WuMing-Chih HoChien-Hung ChenHong-Shiee LaiPo-Huang Lee<h4>Background & aims</h4>Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of hepatocellular carcinoma (HCC) was accompanied by a significant reduction in serum IGF-1 levels. Here, we hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1 expression post-transcriptionally.<h4>Methods</h4>The miRNAs expression profiles in a dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA (miR)-190b, which was significantly up-regulated in HCC tumor tissues when compared with paired non-tumor tissues, was among those predicted to interact with 3'-untranslated region (UTR) of IGF-1. In order to explore the regulatory effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative real-time PCR, western blotting and immunofluorecence analysis were performed in HCC cells.<h4>Results</h4>Overexpression of miR-190b in Huh7 cells attenuated the expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and functional target of miR-190b. Additionally, low serum IGF-1 level was associated with insulin resistance and poor overall survival in HCC patients.<h4>Conclusions</h4>Increased expression of miR-190 may cause decreased IGF-1 in HCC development. Insulin resistance appears to be a part of the physiopathologic significance of decreased IGF-1 levels in HCC progression. This study provides a novel miRNA-mediated regulatory mechanism for controlling IGF-1 expression in HCC and elucidates the biological relevance of this interaction in HCC.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089446&type=printable |
| spellingShingle | Tzu-Min Hung Cheng-Maw Ho Yen-Chun Liu Jia-Ling Lee Yow-Rong Liao Yao-Ming Wu Ming-Chih Ho Chien-Hung Chen Hong-Shiee Lai Po-Huang Lee Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. PLoS ONE |
| title | Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. |
| title_full | Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. |
| title_fullStr | Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. |
| title_full_unstemmed | Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. |
| title_short | Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. |
| title_sort | up regulation of microrna 190b plays a role for decreased igf 1 that induces insulin resistance in human hepatocellular carcinoma |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089446&type=printable |
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