title: Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism.
abstract: This study explored the effects of microRNA-3178 (miR-3178) on hepatocellular carcinoma (HCC) tumor endothelial cells (TECs) and on the target mRNA. Real-time polymerase chain reaction (PCR) was performed to detect the differential expression of miR-3178 in hepatic sinusoidal endothelial cells (HSECs) and HCC TECs. Furthermore, HCC TECs were transfected with miR-3178 mimic/inhibitor or their respective negative controls. The expression of miR-3178 before and after transfection was confirmed through RT-PCR. The effects of miR-3178 on the proliferation, apoptosis, cell cycle, invasion, migration, and angiogenesis of HCC TECs were also investigated through methyl thiazol tetrazolium assay, flow cytometry, matrigel invasion assay, transwell migration assay, and tube formation assay. Early growth responsive gene 3 (EGR3), as the putative target of miR-3178, was detected through RT-PCR and Western blot. Compared with HSECs, HCC TECs had lower miR-3178 expression levels (P < 0.001). MiR-3178 mimic inhibited proliferation, arrested cell cycle in G1 phase, and increased apoptosis. The numbers of migrated and invaded cells and capillary-like structures were significantly less in the mimic group than in the other groups. MiR-3178 mimic significantly decreased the mRNA and protein expression levels of EGR3. By contrast, miR-3178 inhibitor induced opposite effects. We conclude that miR-3178 was lowly expressed in HCC TECs, and miR-3178 mimic specifically inhibited the proliferation, migration, invasion, and angiogenesis and promoted the apoptosis and G1 phase arrest of HCC TECs in vitro through the inhibition of EGR3 expression. Thus, miR-3178 might be a critical target in HCC therapy.
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China. Electronic address: shenshiqiang2014@hotmail.com.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Zubing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Ruichen
authors.initials: R
authors.lastname: Yan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015197:Carcinogenicity Tests / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D051776:Early Growth Response Protein 3 / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics
chemical_list: C079945:EGR3 protein, human; C000602532:MIRN3178 microRNA, human; D035683:MicroRNAs; D051776:Early Growth Response Protein 3
keywords: Angiogenesis; Apoptosis; Cell cycle; EGR3; Hepatic sinusoidal endothelial cells; Hepatocellular carcinoma; Invasion; MiR-3178; Migration; Proliferation; Tumor vascular endothelial cells