title: RIG-I suppresses the migration and invasion of hepatocellular carcinoma cells by regulating MMP9.
abstract: The retinoic acid-induced protein I (Rig-I/Ddx58), (RIG-I) initiates a signaling cascade that induces innate immune defences which is associated with the production of type I interferons (IFNs) and inflammatory cytokines to establish an antiviral state. Aberrant RIG-I signaling leads to inflammation, autoimmune diseases and cancer. However, the role of RIG-I in hepatocellular carcinoma (HCC) is still unknown. Here, we observed that RIG-I expression was downregulated in HCC tissues and loss of RIG-I expression was correlated with poor clinicopathological features. Additionally, we demonstrated that patients with positive RIG-I expression had a better 3-year survival and RIG-I was an independent factor for predicting the prognosis of HCC patients. Elevated RIG-I expression inhibited the proliferation, migration, and invasion of HCC. Inhibiting RIG-I with its specific siRNA was able to attenuate the malignant behavior of HCC cells. Moreover, RIG-I inhibited the invasive behavior through downregulating matrix metalloproteinase-9 (MMP9). Mechanistically, RIG-I enhances IFN-α response by amplifying IFN-α effecter signaling via strengthening STAT1 activation. Addressing this pathway, we identified that RIG-I may serve as a prognostic marker and that MMP9 may be a potential target of RIG-I in HCC.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D011971:Receptors, Immunologic; D016019:Survival Analysis
chemical_list: D011971:Receptors, Immunologic; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases