title: Downregulation of GRIM-19 is associated with hyperactivation of p-STAT3 in hepatocellular carcinoma.
abstract: Accumulating evidence has implicated that constitutive activation of signal transducer and activator of transcription protein 3 (STAT3) may be a major oncogenic factor involved in hepatocellular carcinoma (HCC) development. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been shown to be a tumor suppressor associated with growth control and suppression of STAT3 activity. The downregulation of GRIM-19 expression has been shown in a number of human tumor types, and it has been correlated with hyperactivation of STAT3. However, the role of GRIM-19 in the pathogenesis of HCC has not been evaluated. The aim of our study was to evaluate GRIM-19 expression levels and investigate their correlation with phosphorylated STAT3 (p-STAT3) levels in HCC. GRIM-19 and p-STAT3 expression levels were analyzed in HCC and adjacent nontumorous liver tissues (ANLT) by immunohistochemistry, western blot analysis, and RT-PCR. GRIM-19 protein expression was predominantly located in the cytoplasm with weak staining in the nucleus in ANLT, but only located in the cytoplasm in HCC tissues. HCC samples exhibited low levels of GRIM-19 and moderate to high levels of p-STAT3 expression. In contrast, ANLT was characterized by high levels of GRIM-19 and low levels of p-STAT3 expression. Downregulation of GRIM-19 was closely correlated with increased histological grade in HCC. GRIM-19 expression is closely correlated with histological grading and p-STAT3 in HCC. Thus, the potential role of GRIM-19 in HCC development may be through these correlations.
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, 250021, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Wanhua
authors.initials: W
authors.lastname: Ren
authors.forename: Yanda
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fu
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Ji
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chengyong
authors.initials: C
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D060787:Neoplasm Grading; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human