title: Bioinformatic identification of IGF1 as a hub gene in hepatocellular carcinoma (HCC) and in-vitro analysis of the chemosensitizing effect of miR-379 via suppressing the IGF1/IGF1R signaling pathway.
abstract: We investigated the interactions among the dysregulated genes in hepatocellular carcinoma (HCC) and identified the hub genes in the protein-protein interaction (PPI) network. Also, we also investigated the regulative effect of miR-379 on the IGF1/IGF1R signaling pathway and chemoresistance in HCC.
  
  
  
  Raw data of a microarray that compared transcriptional gene profile between 3-paired HCC tissue samples and adjacent normal tissues were downloaded from Expression Atlas (E-GEOD-33006). The raw data was reanalyzed to identify the significantly dysregulated genes, which were further used for PPI network and KEGG pathway analysis. The regulative effect of miR-379 on IGF1R expression was studied by dual luciferase assay and Western blotting. The functional role of miR-379 in chemosensitivity of HCC cells was studied by drug sensitivity and flow cytometric assay.
  
  
  
  IGF1 is a hub gene that is mostly upregulated in HCC and it is an important player in the p53 signaling pathway. Knockdown of IGF1R significantly decreased IC50 of 5-FU, paclitaxel (PTX) and Doxorubicin (DOX) in Huh7 and HepG2 cells. MiR-379 could directly bind to the 3'UTR of IGF1R and suppress IGF1R expression. MiR-379 overexpression sensitized Huh7 and HepG2 cells to 5-FU, PTX and DOX and also enhanced DOX-induced cell apoptosis.
  
  
  
  IGF1 is a hub gene in HCC and is also one of the most upregulated genes in HCC tissues compared to normal tissues. It is involved in the p53 signaling pathway regulation. MiR-379 can sensitize HCC cells to chemotherapeutic reagents via targeting IGF1R and suppressing its expression.
authors.affiliation: Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China. liyanhao@fimmu.com.
authors.forename: D-J
authors.initials: DJ
authors.lastname: Huang
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Li
authors.forename: Y-C
authors.initials: YC
authors.lastname: Luo
authors.forename: H-Y
authors.initials: HY
authors.lastname: He
authors.forename: H-J
authors.initials: HJ
authors.lastname: Huang
mesh_terms: D006528:Carcinoma, Hepatocellular; D019295:Computational Biology; D006801:Humans; D007334:Insulin-Like Growth Factor I; D008113:Liver Neoplasms; D035683:MicroRNAs / Q000235:genetics
chemical_list: D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I