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新型 KDM2B/SAV1 信号通路促进胃癌的进展。

Novel KDM2B/SAV1 Signaling Pathway Promotes the Progression of Gastric Cancer.

机构信息

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Genet Res (Camb). 2023 Mar 31;2023:1230182. doi: 10.1155/2023/1230182. eCollection 2023.

Abstract

Salvador homologue 1 (SAV1), which is reported to act as a tumor suppressor in different types of cancer, is one of the key components of the Hippo pathway. However, the expression and mechanisms of SAV1 in the development and progression of gastric cancer (GC) remain to be elucidated. Immunohistochemistry (IHC) was performed in the present study to assess the expression levels of SAV1 and lysine-specific demethylase 2B (KDM2B) in GC tissues. The biological effects of SAV1 on GC cell proliferation, migration, and invasion were studied . KDM2B transcriptionally regulates SAV1 expression in several GC cell lines, and molecular experiments were performed to investigate underlying mechanisms. The expression level of SAV1 was significantly decreased in GC tissues and cell lines, negatively associated with tumor invasion depth, lymph node metastasis, and TNM stage, and positively associated with the overall survival of patients with GC. SAV1 overexpression inhibited the proliferation, migration, and invasion of GC cells. Further mechanistic studies revealed that KDM2B transcriptionally regulated SAV1 expression and further regulated the Hippo signaling pathway. To conclude, the present study demonstrated that KDM2B transcriptionally regulated SAV1 expression and promoted GC progression.

摘要

Salvador 同源物 1(SAV1)被报道在不同类型的癌症中作为肿瘤抑制因子发挥作用,是 Hippo 通路的关键组成部分之一。然而,SAV1 在胃癌(GC)发展和进展中的表达和机制仍有待阐明。本研究通过免疫组织化学(IHC)检测了 GC 组织中 SAV1 和赖氨酸特异性去甲基化酶 2B(KDM2B)的表达水平。研究了 SAV1 对 GC 细胞增殖、迁移和侵袭的生物学影响。KDM2B 在几种 GC 细胞系中转录调控 SAV1 的表达,并进行了分子实验以研究潜在的机制。SAV1 在 GC 组织和细胞系中的表达水平显著降低,与肿瘤浸润深度、淋巴结转移和 TNM 分期呈负相关,与 GC 患者的总生存率呈正相关。SAV1 过表达抑制了 GC 细胞的增殖、迁移和侵袭。进一步的机制研究表明,KDM2B 转录调控 SAV1 的表达,并进一步调控 Hippo 信号通路。综上所述,本研究表明 KDM2B 转录调控 SAV1 的表达并促进 GC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8cf/10081913/a4bcfadc95ab/GR2023-1230182.001.jpg

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