title: Mcl-1 Is a Novel Target of miR-26b That Is Associated with the Apoptosis Induced by TRAIL in HCC Cells.
abstract: OBJECTIVE
  To investigate the role of miR-26b and Mcl-1 in TRAIL-inducing cell death in hepatocellular carcinoma. Methods. The expression of miR-26b and Mcl-1 in HCC was detected by RT-qPCR and western blot. The regulation of Mcl-1 by miR-26b was determined by luciferase reporter assay. MTT and flow cytometry were employed to detect the cell viability and apoptosis.
  
  
  RESULTS
  miR-26b is commonly downregulated in HCC cell lines compared with the LO2 cell line. In contrast, the Mcl-1 expression is upregulated in HCC cell lines. Bioinformatic analysis identified a putative target site in the Mcl-1 mRNA for miR-26b and luciferase reporter assay showed that miR-26b directly targeted the 3'-UTR (3'-Untranslated Regions) of Mcl-1 mRNA. Transfection of miR-26b mimics suppressed Mcl-1 expression in HCC cells and sensitized the cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) cytotoxicity. In addition, transfection of HCC cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-26b to TRAIL-inducing apoptosis.
  
  
  CONCLUSIONS
  Our study showed that miR-26b was a negative regulator of Mcl-1 gene and sensitized TRAIL-inducing apoptosis in HCC cells, suggesting that the miR-26b-Mcl-1 pathway might be a novel target for the treatment of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China.
authors.forename: Baoxian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis* / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C579095:MCL1 protein, human; C528163:MIRN26 microRNA, human; C505653:TNFSF10 protein, human