title: Down-Regulated NRSN2 Promotes Cell Proliferation and Survival Through PI3K/Akt/mTOR Pathway in Hepatocellular Carcinoma.
abstract: OBJECTIVE
  Neurensin-2 (NRSN2) is a neuronal membrane protein; previous reports indicated that it might function as a tumor suppressor in hepatocellular carcinoma (HCC). However, its biological functions and associated mechanisms remain unknown. In the current study, we aimed to investigate the biological functions and possible mechanisms of neurensin-2.
  
  
  METHODS
  The mRNA and protein level of NRSN2 in HCC has tissues and cell lines were detected by quantitative real-time PCR, immunohistochemistry staning and western blot. Overexpressing and silencing the level of NRSN2 in HCC cell lines were used to investigate the role of NRSN2 in HCC. CCK-8 assays, SA-β gel staining, Annexin V/PI staining, quantitative real-time PCR and western blot were employed to explore the role and mechanisms of HCC.
  
  
  RESULTS
  NRSN2 was more commonly down-regulated HCC tissues compared with adjacent tissues, and the expression pattern of NRSN2 was not only closely correlated with tumor size and TNM stage but also negatively correlated with patient prognosis. Both loss and gain function assays revealed that NRSN2 inhibits cancer cell proliferation and promotes cancer cell senescence and apoptosis. We further found that NRSN2 might regulate PI3K/AKT signaling and p53/p21 pathway to exert its role in HCC cell proliferation, senescence and apoptosis.
  
  
  CONCLUSIONS
  Our study validates the suppressive role of NRSN2 in both clinicopathologic and biological aspects in HCC tumorigenesis.
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Longzhi
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. qiangxiadds@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D016009:Chi-Square Distribution; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C546648:NRSN2 protein, human; C546842:MTOR protein, human
keywords: Apoptosis; Cell proliferation; Cell senescence; Hepatocellular carcinoma; Neurensin-2; Patient prognosis