title: RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX signaling and predicted poor postsurgical prognosis in HCC.
abstract: Although growing body of evidences have identified a critical role for receptor-interacting protein kinase 1 (RIP1) in mediating cell death signaling, its possible contribution to hepatocellular carcinoma (HCC) progression remains unclear. Here, we displayed that expression of RIP1 was significantly upregulated in HCC tissues than in adjacent liver tissues from 81.9 % HCC patients (P < 0.001) by immunohistochemistry (IHC) staining. Overexpression of RIP1 was found positively associated with HBV infection, advanced TNM staging, portal vein invasion, and intrahepatic metastases. Kaplan-Meier curve analysis indicated that patients with higher RIP1 expression in HCC tissues suffered from unfavorable postsurgical survival. Higher RIP1 expression in HCC tissues was also confirmed to be an independent poor prognostic predictor. Knockdown of RIP1 resulted in suppression of cell viability and proliferation and induced cell apoptosis in MHCC97h cells. Nevertheless, enforced expression of RIP1 promoted cell viability and proliferation of Huh7 cells and inhibited cell apoptosis. Mechanistic studies revealed that RIP1 exerted its function on HCC progression via activating AKT/Bcl-2/BAX signaling. In conclusion, our results provided the evidence of RIP1 overexpression in HCC, and RIP1 could be a novel predictive factor of unfavorable prognosis in HCC patients. Activation of AKT/Bcl-2/BAX signaling contributed to RIP1 promoting HCC progression.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China. raymondzhengxin@foxmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C119724:AGFG1 protein, human; C494826:BAX protein, human; D014408:Biomarkers, Tumor; D028861:Nuclear Pore Complex Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051028:bcl-2-Associated X Protein; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Bcl-2/BAX; HCC; Prognosis; RIP1