title: MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma.
abstract: Aberrant expression of microRNAs (miRNAs) plays fundamental effect on the pathogenesis of hepatocellular carcinoma (HCC). MiR-27b was previously found to play important roles in human cancers. However, its expression status, clinical significance, and biological functions in HCC remain largely unclear. The expression status of miR-27b in HCC specimens and cells were determined with qRT-PCR. MTT, 5-bromodeoxyuridine (BrdU) proliferation assays, and flow cytometry analysis were carried out to assay proliferation, cell cycle, and apoptosis. A subcutaneous model was used to evaluated the HCC tumor growth in vivo. The putative target gene of miR-27b was disclosed by TargetScan and a luciferase reporter assay. The levels of miR-27b were overexpressed in HCC. Overexpression of miR-27b was correlated with adverse prognostic features and reduced survival rate. Inhibition of miR-27b in SMMC-7721 cells remarkably suppressed proliferative ability and cell-cycle progression while enhanced apoptosis. In contrast, miR-27b overexpression resulted in prominent increased proliferation and process of cell cycle and reduced apoptosis of Hep3B cells. In vivo studies showed that knockdown of miR-27b inhibited the in vivo growth of SMMC-7721 cells in mouse xenograft model. Furthermore, we confirmed that Fbxw7 was directly regulated by miR-27b and mediated the roles of miR-27b in HCC. We suggest that miR-27b serves as an oncogenic miRNA in HCC by modulating proliferation, cell-cycle progression, and apoptosis, and its oncogenic effect is mediated by its downstream target gene, Fbxw7.
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China.
authors.forename: Xin-Fang
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Hou
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Huaihe Hospital, Henan University, No. 8 Baobei Road, Kaifeng, Henan Province, 475000, China. gequan_xing@163.com.
authors.forename: Quan-Xing
authors.initials: QX
authors.lastname: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009857:Oncogenes; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases
keywords: Cell growth; Fbxw7; Hepatocellular carcinoma; MicroRNA-27b; Oncogenic microRNA