title: APRIL induces cisplatin resistance in gastric cancer cells via activation of the NF-κB pathway.
abstract: BACKGROUND
  A proliferation-inducing ligand (APRIL) is a tumor-necrosis factor (TNF) family member and is a novel cytokine crucial in sustaining lymphocytic leukemia B cell survival and proliferation. However, its role in gastric cancer (GC) remains unclear. In this study, we investigated the expression pattern and prognostic role of APRIL in GC.
  
  
  METHODS
  Expression of APRIL was assessed by immunohistochemistry and real-time PCR. Prognostic role of APRIL expression was evaluated. We also discovered the effect of APRIL on chemo-resistance in GC cells and the underlying mechanisms.
  
  
  RESULTS
  APRIL mRNA levels were significantly increased in GC tissues compared with adjacent tissues and high expression levels of APRIL in tumor cells significantly correlated with poor overall survival in patients receiving cisplatin adjuvant treatment. Overexpression of APRIL in AGS cells significantly attenuated the therapeutic efficacy of cisplatin in vitro and in vivo. In contrast, silence of APRIL in SGC7901 cells enhanced cisplatin-induced tumor suppression. Our data further revealed that the canonical NF-κB pathway was involved in APRIL-mediated chemo-resistance. In addition, expression of APRIL was regulated by miR-145 in GC cells.
  
  
  CONCLUSIONS
  APRIL is a novel clinical chemo-resistance biomarker for gastric cancer and might be a promising therapeutic target for GC patients.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhi
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Tao
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xiang
authors.forename: Hongyong
authors.initials: H
authors.lastname: Cao
authors.forename: Zijun
authors.initials: Z
authors.lastname: Liu
authors.forename: Kunxing
authors.initials: K
authors.lastname: Yang
authors.forename: Chengyu
authors.initials: C
authors.lastname: Lv
authors.forename: Shaozhong
authors.initials: S
authors.lastname: Ni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D002945:Cisplatin