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SUZ12 在肺腺癌中的表达及作用。

The expression and role of SUZ12 in lung adenocarcinoma.

机构信息

Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Department of Oncology, the Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Cancer Med. 2024 Oct;13(19):e70190. doi: 10.1002/cam4.70190.

Abstract

BACKGROUND

SUZ12 is one of the core members of the polycomb repressive complex 2 (PRC2), but its expression and role in lung adenocarcinoma (LUAD) are unclear. We aimed to explore the expression, prognosis, biological functions and roles of SUZ12 in LUAD.

METHODS

The expression of SUZ12 was detected by immunohistochemical staining, qRT-PCR, and western blotting in LUAD tissues and cells. The biological functions and molecular mechanisms of SUZ12 were characterized by a range of in vitro and in vivo experiments.

RESULTS

SUZ12 was overexpressed in LUAD tissues, and high SUZ12 expression was correlated with worse clinicopathological features and a poorer prognosis. Knockdown of SUZ12 significantly inhibited cell growth, colony formation, invasion, and migration, and induced apoptosis and G1/S phase arrest, while overexpression of SUZ12 had the opposite effects. Knockdown of SUZ12 decreased the tumorigenic capacity of A549 cells in vivo. The expression of key signaling molecules related to the cell cycle, apoptosis, migration, and immunity were altered by the knockdown or overexpression of SUZ12. SUZ12 can directly bind to the Bax promoter region, EZH2 and H3K27me3 levels dependents on SUZ12. The expression levels of SUZ12 and Bax were negatively correlated in LUAD tissues.

CONCLUSIONS

SUZ12 is a new oncogene related to the poor prognosis of LUAD. SUZ12 regulates LUAD progression by regulating the expression of related signaling molecules, and as a part of the PRC2 complex, it may bind to the Bax promoter to silence Bax expression.

摘要

背景

SUZ12 是多梳抑制复合物 2(PRC2)的核心成员之一,但它在肺腺癌(LUAD)中的表达和作用尚不清楚。我们旨在探讨 SUZ12 在 LUAD 中的表达、预后、生物学功能和作用。

方法

通过免疫组织化学染色、qRT-PCR 和 Western blot 检测 LUAD 组织和细胞中 SUZ12 的表达。通过一系列体外和体内实验来描述 SUZ12 的生物学功能和分子机制。

结果

SUZ12 在 LUAD 组织中过表达,高 SUZ12 表达与更差的临床病理特征和预后不良相关。SUZ12 敲低显著抑制细胞生长、集落形成、侵袭和迁移,并诱导细胞凋亡和 G1/S 期阻滞,而过表达 SUZ12 则产生相反的效果。SUZ12 敲低降低了 A549 细胞在体内的致瘤能力。SUZ12 的敲低或过表达改变了与细胞周期、凋亡、迁移和免疫相关的关键信号分子的表达。SUZ12 可以直接结合 Bax 启动子区域,EZH2 和 H3K27me3 水平依赖于 SUZ12。SUZ12 和 Bax 在 LUAD 组织中的表达水平呈负相关。

结论

SUZ12 是一个与 LUAD 预后不良相关的新的癌基因。SUZ12 通过调节相关信号分子的表达来调节 LUAD 的进展,并且作为 PRC2 复合物的一部分,它可能结合到 Bax 启动子上沉默 Bax 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e2/11471883/3c553b607863/CAM4-13-e70190-g001.jpg

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