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下调 TRIM27 通过抑制 Hippo-BIRC5 通路抑制胃癌细胞增殖。

Downregulation of TRIM27 suppresses gastric cancer cell proliferation via inhibition of the Hippo-BIRC5 pathway.

机构信息

Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China.

Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China.

出版信息

Pathol Res Pract. 2020 Sep;216(9):153048. doi: 10.1016/j.prp.2020.153048. Epub 2020 Jun 8.

Abstract

Although tripartite motif containing 27 (TRIM27) protein has been implicated in the progression of many cancer types, its role in gastric cancer (GC) remains poorly understood. Given that TRIM27 may be associated with the baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) gene, which is downstream of the Hippo pathway, we clarified their relationship in GC progression. In vitro cultures of 7 GC cell lines, 92 GC patient tumor samples and 46 normal clinical samples were used to examine the influence of changes in TRIM27 expression, which was assessed by quantitative PCR, immunohistochemistry, western blot analysis, and cell viability assays. We found that TRIM27 overexpression was correlated with tumor size, depth of invasion, and poor GC prognosis, while TRIM27 small interfering RNA knockdown inhibited cell proliferation and colony formation, induced apoptosis, and increased sensitivity towards 5-fluorouracil treatment in MGC-803 and HGC-27 GC cell lines. Notably, TRIM27 downregulation resulted in BIRC5 suppression via large tumor suppressor kinase 2 (LATS2) upregulation and subsequent Yes-associated protein 1 (YAP1) inhibition in MGC-803 and HGC-27 GC cell lines. In conclusion, our findings revealed the positive correlation between TRIM27 and GC progression through mediation of the Hippo-BIRC5 axis in GC.

摘要

尽管三结构域蛋白 27(TRIM27)蛋白已被牵涉到许多癌症类型的进展中,但它在胃癌(GC)中的作用仍知之甚少。鉴于 TRIM27 可能与凋亡抑制因子重复包含 5(BIRC5)基因有关,BIRC5 基因是 Hippo 通路的下游基因,我们阐明了它们在 GC 进展中的关系。我们使用 7 种 GC 细胞系的体外培养物、92 名 GC 患者肿瘤样本和 46 名正常临床样本,通过定量 PCR、免疫组织化学、western blot 分析和细胞活力测定来检查 TRIM27 表达变化的影响。我们发现,TRIM27 的过表达与肿瘤大小、浸润深度和 GC 不良预后相关,而 TRIM27 的小干扰 RNA 敲低抑制了 MGC-803 和 HGC-27 GC 细胞系的细胞增殖和集落形成,诱导了细胞凋亡,并增加了对 5-氟尿嘧啶治疗的敏感性。值得注意的是,在 MGC-803 和 HGC-27 GC 细胞系中,TRIM27 的下调通过大肿瘤抑制激酶 2(LATS2)的上调和随后 Yes 相关蛋白 1(YAP1)的抑制导致 BIRC5 的抑制。总之,我们的研究结果揭示了 TRIM27 通过 Hippo-BIRC5 轴在 GC 中对 GC 进展的正相关。

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