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染色体盒同源物7通过抑制ERK/MAPK信号通路在肺腺癌和肺鳞状细胞癌中发挥肿瘤抑制作用。

Chromobox Homologue 7 Acts as a Tumor Suppressor in Both Lung Adenocarcinoma and Lung Squamous Cell Carcinoma via Inhibiting ERK/MAPK Signaling Pathway.

作者信息

Huang Jinlong, Zhang Weiqing, Lin Dongliang, Lian Luoyu, Hong Wenshan, Xu Zhendong

机构信息

Department of Thoracic Surgery, Quanzhou First Hospital, Quanzhou, China.

出版信息

Evid Based Complement Alternat Med. 2022 May 19;2022:4952185. doi: 10.1155/2022/4952185. eCollection 2022.

Abstract

Chromobox homologue 7 (CBX7) is a member of the polycomb group family that plays a pivotal role in regulating cellular processes in human cancers. This study aims to explore the function and underlying molecular mechanisms of CBX7 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The expression of CBX7 in LUAD and LUSC tissues was analyzed by UALCAN and GEPIA based on the TCGA database. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays, respectively. Cell migration and invasion were detected by transwell assay. The functions of downregulated genes in LUAD were enriched via GO and KEGG pathway analyses. The mRNA expression of CBX7, ERK1/2, and p38 was determined by qRT-PCR, and the protein levels of CBX7, ERK1/2, p-ERK1/2, p38, and p-p38 were measured by Western blotting. Tumor xenograft model was established to validate the antitumor effect of CBX7. The expression of CBX7 and Ki-67 in tumor tissues was detected by immunohistochemistry. CBX7 was downregulated in the tissues and cells of both LUAD and LUSC. Low CBX7 expression was associated with a poor overall survival rate in LUAD patients. CBX7 overexpression inhibited the viability, migration, and invasion and promoted the apoptosis of LUAD and LUSC cells. In addition, the downregulated genes in LUAD were enriched in MAPK cascade (GO) and MAPK signaling pathway (KEGG). ERK/MAPK pathway was then determined as a downstream target of CBX7, which was inhibited by CBX7 overexpression in LUAD and LUSC cells. The overexpression of CBX7 inhibited the malignant progression of LUAD and LUSC cells probably via suppressing the ERK/MAPK signaling pathway and .

摘要

染色质盒同源物7(CBX7)是多梳蛋白家族的成员,在调节人类癌症中的细胞过程中起关键作用。本研究旨在探讨CBX7在肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)中的功能及潜在分子机制。基于TCGA数据库,通过UALCAN和GEPIA分析CBX7在LUAD和LUSC组织中的表达。分别采用CCK-8和流式细胞术检测细胞活力和凋亡情况。通过Transwell实验检测细胞迁移和侵袭能力。通过GO和KEGG通路分析对LUAD中下调基因的功能进行富集。采用qRT-PCR检测CBX7、ERK1/2和p38的mRNA表达,通过蛋白质免疫印迹法检测CBX7、ERK1/2、p-ERK1/2、p38和p-p38的蛋白水平。建立肿瘤异种移植模型以验证CBX7的抗肿瘤作用。通过免疫组织化学检测肿瘤组织中CBX7和Ki-67的表达。CBX7在LUAD和LUSC的组织及细胞中均呈下调表达。CBX7低表达与LUAD患者的总生存率较低相关。CBX7过表达抑制了LUAD和LUSC细胞的活力、迁移和侵袭,并促进其凋亡。此外,LUAD中下调的基因在MAPK级联反应(GO)和MAPK信号通路(KEGG)中富集。ERK/MAPK通路随后被确定为CBX7的下游靶点, 在LUAD和LUSC细胞中,CBX7过表达可抑制该通路。CBX7过表达可能通过抑制ERK/MAPK信号通路来抑制LUAD和LUSC细胞的恶性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c56a/9135519/63bc1263f476/ECAM2022-4952185.001.jpg

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