Department of Oncological Surgery, Minhang Branch of Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
J Cancer Res Clin Oncol. 2021 Jun;147(6):1685-1697. doi: 10.1007/s00432-021-03574-x. Epub 2021 Mar 18.
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.
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.
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.
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.
背景/目的：增殖诱导配体（APRIL，也称为 TNFSF13、CD256）是肿瘤坏死因子（TNF）超家族的一员，参与多种疾病。在这项工作中，我们探讨了胃癌患者中 APRIL 的表达与 H. pylori 感染之间的潜在关联和潜在机制。
我们通过免疫组织化学染色分析了 200 个 GC 组织样本中的 APRIL 表达水平。通过改良的吉姆萨染色检测 H. pylori 感染。通过 CCK-8 测定、集落形成、流式细胞术检测、Transwell 迁移测定、Matrigel 侵袭测定和动物肿瘤异种移植测定，测试了 APRIL 对人 GC 细胞的体外和体内的生物学效应。
APRIL 反应性与体外和体内的 H. pylori 感染呈正相关。事实证明，miR-145 的表达减少与 H. pylori 感染呈剂量和时间依赖性，与 APRIL 表达一致。miR-145 显著减弱了 H. pylori 感染对 SGC7901 和 BGC823 细胞系中 APRIL 基因表达的影响。此外，APRIL 过表达促进了 GC 细胞的增殖、迁移、侵袭和转移，同时减少了凋亡，而 APRIL 敲低则抑制了这些作用。我们证实 APRIL 通过 AKT 的磷酸化激活了经典的 NF-κB 途径。
通过 miR-145，在人类 H. pylori 感染的 GC 中，促进 GC 细胞增殖、迁移、侵袭、活力和转移的 APRIL 表达上调。此外，APRIL 通过激活 NF-κB 途径诱导胃肿瘤发生。这些结果可能为深入分析 APRIL 在 GC 风险和预后中的作用提供了框架。
