title: Overexpression of GRIM-19, a mitochondrial respiratory chain complex I protein, suppresses hepatocellular carcinoma growth.
abstract: GRIM-19 has been demonstrated as an important regulator for the normal tissue development. Recently, more evidences regarded GRIM-19 as the new tumor suppressor. However, the possible mechanisms underlying GRIM-19 suppressing cancer growth are unclear. In the present study, Paired hepatocellular carcinoma (HCC) and adjacent non-tumor liver tissues were obtained from 54 patients who underwent primary surgical HCC tissue resection. GRIM-19 protein expression in HCC tissues was performed by immunohistochemistry. Cells were transfected by lentiviruses plasmid expressing GRIM-19. RT-PCR and Western blot analyses were performed to confirm the expression of GRIM-19 mRNA or protein. Cell proliferation was assessed by MTT and FCM analyses. Mitochondrial membrane potential and apoptosis were respectively determined by using fluorescence microscopy and FCM analyses. AKT1, pAKT1, cyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, and cytochrome C were detected by Western blot and immunofluorescence. GRIM-19 protein expression was markedly lower in HCC than in paired adjacent non-tumor liver tissues. GRIM-19 overexpression in HCC cells significantly induced cell cycle arrest and enhanced apoptosis. We also found that AKT1 expression and phosphorylation were regulated by the expression of GRIM-19. Collectively, our study demonstrated that GRIM-19 overexpression suppressed HCC growth and downregulated AKT1 expression, suggesting that GRIM-19 might play a crucial role in hepatocarcinogenesis through negatively regulating the PI3K/AKT signaling pathway.
authors.affiliation: Department of Gastroenterology, First Hospital of Jilin University Changchun 130021, China ; Department of Pathophysiology, School of Basic Medicine, Jilin University Changchun 130021, China.
authors.forename: Dexia
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Jilin University Changchun 130021, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Jilin University Changchun 130021, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Pathology, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Gastroenterology, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Luoluo
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Jilin University Changchun 130021, China.
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Jilin University Changchun 130021, China.
authors.forename: Hebin
authors.initials: H
authors.lastname: Wang
authors.affiliation: New Vaccine National Engineering Research Center, Beijing Three-Room South Hospital Beijing 100024, China.
authors.forename: Deqi
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Pathology, First Hospital of Jilin University Changchun 130021, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004579:Electron Transport; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D009247:NADH, NADPH Oxidoreductases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; C439057:NDUFA13 protein, human; C494918:AKT1 protein, human
keywords: AKT1; GRIM-19; apoptosis; cell cycle; hepatocellular carcinoma