Up-regulation of MicroRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma
Journal
PLoS ONE
Journal Volume
9
Journal Issue
2
Date Issued
2014
Author(s)
Hung T.-M.
Liu Y.-C.
Lee J.-L.
Liao Y.-R.
Abstract
Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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. ? 2014 Hung et al.
Other Subjects
messenger RNA; microRNA; microRNA 190b; somatomedin C; unclassified drug; messenger RNA; microRNA; MIRN190 microRNA, human; somatomedin C; tumor marker; 3' untranslated region; adult; article; cancer growth; cancer prognosis; cancer survival; clinical article; controlled study; female; gene expression profiling; gene expression regulation; gene interaction; gene overexpression; genetic association; human; human cell; human tissue; IGF 1 gene; immunofluorescence test; insulin resistance; liver cell carcinoma; male; prediction; protein blood level; quantitative analysis; real time polymerase chain reaction; Western blotting; apoptosis; case control study; cell proliferation; comparative study; DNA microarray; enzyme immunoassay; enzyme linked immunosorbent assay; fluorescent antibody technique; genetics; insulin resistance; liver cell carcinoma; liver tumor; metabolism; middle aged; mortality; pathology; prognosis; reverse transcription polymerase chain reaction; survival rate; tumor cell culture; upregulation; Adult; Apoptosis; Blotting, Western; Carcinoma, Hepatocellular; Case-Control Studies; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Insulin Resistance; Insulin-Like Growth Factor I; Liver Neoplasms; Male; MicroRNAs; Middle Aged; Oligonucleotide Array Sequence Analysis; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Tumor Cells, Cultured; Tumor Markers, Biological; Up-Regulation
Publisher
Public Library of Science
Type
journal article