title: Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma.
abstract: The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies - include growth curves, cell death, migration assays and in vivo studies - verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.|Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors: Haoran
authors: H
authors: Peng
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Masaharu
authors: M
authors: Ishida
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Ling
authors: L
authors: Li
authors: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Atsushi
authors: A
authors: Saito
authors: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Atsushi
authors: A
authors: Kamiya
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: James P
authors: JP
authors: Hamilton
authors: Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors: Rongdang
authors: R
authors: Fu
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Alexandru V
authors: AV
authors: Olaru
authors: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, P.R. China.
authors: Fangmei
authors: F
authors: An
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Irinel
authors: I
authors: Popescu
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Razvan
authors: R
authors: Iacob
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Simona
authors: S
authors: Dima
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Sorin T
authors: ST
authors: Alexandrescu
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Razvan
authors: R
authors: Grigorie
authors: Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors: Anca
authors: A
authors: Nastase
authors: Department of Immunology, The Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.|Department of Functional Genomics, The Oncology Institute Ion Chiricuta, Cluj Napoca, Romania.|The Research Center for Functional Genomics, Biomedicine and Translational Medicine, The Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors: Ioana
authors: I
authors: Berindan-Neagoe
authors: The Research Center for Functional Genomics, Biomedicine and Translational Medicine, The Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.|Department of Hematology, The Oncology Institute Ion Chiricuta, Cluj Napoca, Romania.
authors: Ciprian
authors: C
authors: Tomuleasa
authors: Department of Surgery, The Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.|Department of Surgery, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Cluj Napoca, Romania.
authors: Florin
authors: F
authors: Graur
authors: Department of Surgery, The Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.|Department of Surgery, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Cluj Napoca, Romania.
authors: Florin
authors: F
authors: Zaharia
authors: Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Michael S
authors: MS
authors: Torbenson
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Esteban
authors: E
authors: Mezey
authors: Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors: Minqiang
authors: M
authors: Lu
authors: Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, USA.|The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors: Florin M
authors: FM
authors: Selaru
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011544:Pseudogenes; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C121427:INTS6 protein, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D025521:Tumor Suppressor Proteins
keywords: INTS6; competitive endogenous RNA; hepatocellular carcinoma; pseudogene; tumor suppressor