Qun Zhang1, Ying Ni2, Xiaofei Zhi3, Jiwei Wang4, Zheng Li4, Jie Tang5, Linjun Wang4, Weizhi Wang4, Zekuan Xu6. 1. Department of Oncological Surgery, Minhang Branch of Fudan University Shanghai Cancer Center, Shanghai, China. 2. Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. 3. Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. 4. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 5. Department of Pediatric Surgery, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China. 6. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. xuzekuan@njmu.edu.cn.
Abstract
BACKGROUND/AIMS: A proliferation-inducing ligand (APRIL, also known as TNFSF13, CD256) is a member of the tumor necrosis factor (TNF) superfamily and involved in a diverse set of diseases. In this work, we explored the potential associations and underlying mechanism in patients suffered from gastric cancer between the expression of APRIL and H. pylori infection. METHODS: We analyzed APRIL expression levels in 200 GC tissue samples by immunohistochemistry staining. H. pylori infection was detected by modified Giemsa staining. The biological effects of APRIL on human GC cells in vitro and in vivo were tested by CCK-8 assay, colony formation, flow cytometry detection, transwell migration assay, matrigel invasion assay, and tumor xenograft assay in animals. RESULTS: APRIL reactivity was positively correlated with H. pylori infection in vitro and vivo. It turned out that the decrease of miR-145 expression was dose-dependent and time-dependent on H. pylori infection and in consistent with APRIL expression. MiR-145 significantly attenuated the effect of H. pylori infection on APRIL gene expression in SGC7901 and BGC823 cell lines. Furthermore, APRIL overexpression promoted the proliferation, migration, invasion, and transfer of GC cells and decreased apoptosis, while APRIL knockdown suppressed these effects. We confirmed that APRIL activated the canonical NF-κB pathway through phosphorylation of AKT. CONCLUSION: The expression of APRIL, which promoted the proliferation, migration, invasion, viability, and metastasis of GC cells, was upregulated in human H. pylori-infected GC through miR-145. Besides, APRIL-induced gastric tumorigenicity via activating NF-κB pathway. These results may provide a framework for the deeper analysis of APRIL in GC risk and prognosis.
BACKGROUND/AIMS: A proliferation-inducing ligand (APRIL, also known as TNFSF13, CD256) is a member of the tumor necrosis factor (TNF) superfamily and involved in a diverse set of diseases. In this work, we explored the potential associations and underlying mechanism in patients suffered from gastric cancer between the expression of APRIL and H. pyloriinfection. METHODS: We analyzed APRIL expression levels in 200 GC tissue samples by immunohistochemistry staining. H. pyloriinfection was detected by modified Giemsa staining. The biological effects of APRIL on human GC cells in vitro and in vivo were tested by CCK-8 assay, colony formation, flow cytometry detection, transwell migration assay, matrigel invasion assay, and tumor xenograft assay in animals. RESULTS: APRIL reactivity was positively correlated with H. pyloriinfection in vitro and vivo. It turned out that the decrease of miR-145 expression was dose-dependent and time-dependent on H. pyloriinfection and in consistent with APRIL expression. MiR-145 significantly attenuated the effect of H. pyloriinfection on APRIL gene expression in SGC7901 and BGC823 cell lines. Furthermore, APRIL overexpression promoted the proliferation, migration, invasion, and transfer of GC cells and decreased apoptosis, while APRIL knockdown suppressed these effects. We confirmed that APRIL activated the canonical NF-κB pathway through phosphorylation of AKT. CONCLUSION: The expression of APRIL, which promoted the proliferation, migration, invasion, viability, and metastasis of GC cells, was upregulated in human H. pylori-infected GC through miR-145. Besides, APRIL-induced gastric tumorigenicity via activating NF-κB pathway. These results may provide a framework for the deeper analysis of APRIL in GC risk and prognosis.
Authors: Paola Bertuccio; Liliane Chatenoud; Fabio Levi; Delphine Praud; Jacques Ferlay; Eva Negri; Matteo Malvezzi; Carlo La Vecchia Journal: Int J Cancer Date: 2009-08-01 Impact factor: 7.396
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Authors: M Hahne; T Kataoka; M Schröter; K Hofmann; M Irmler; J L Bodmer; P Schneider; T Bornand; N Holler; L E French; B Sordat; D Rimoldi; J Tschopp Journal: J Exp Med Date: 1998-09-21 Impact factor: 14.307