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CCT8在泛癌中的致癌价值的多组学分析与验证

Multi-Omics Analysis and Verification of the Oncogenic Value of CCT8 in Pan-Cancers.

作者信息

Gong Lian, Zhong Ming, Gong Kai, Wang Zhanwang, Zhong Yong, Jin Yi, Chen Haotian, Tai Panpan, Chen Xinyu, Chen Aiyan, Cao Ke

机构信息

Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China.

Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China.

出版信息

J Inflamm Res. 2023 May 29;16:2297-2315. doi: 10.2147/JIR.S403499. eCollection 2023.

Abstract

BACKGROUND

Chaperonin-containing TCP1 subunit 8 (CCT8) has been proved to be involved in the occurrence and development of some cancers. However, no study has reported the potential role of CCT8 in a pan-cancer manner.

METHODS

TIMER2.0, GEPIA2, UALCAN and Sangerbox were used to explore the expression, prognosis and methylation of CCT8. We used cBioPortal, TISIDB, SangerBox, TIMER2.0 and TISMO to investigate the genetic alteration of CCT8 and the relationship of CCT8 with molecular subtype, immune subtype, immune infiltration and immunotherapy response. CCT8-related genes were screened out through GEPIA and STRING for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CCK-8, the colony formation assay, the wound healing assay and the Transwell assay were performed to explore the influence of CCT8 on proliferation and migration.

RESULTS

CCT8 was highly expressed in most cancers with a poor prognosis. The expression level of CCT8, which was affected by the promoter region methylation and genetic alteration, was related to the molecular and immune subtype of cancers. Interestingly, CCT8 was positively associated with the activated CD4 T cells and type 2 T-helper cells. CCT8 played a vital role in the cell cycle and RNA transport of cancers, and it significantly inhibited the proliferation and migration of lung adenocarcinoma cells when it was knocked down.

CONCLUSION

CCT8 plays an indispensable role in promoting the proliferation and migration of many cancers. CCT8 might be a biomarker of T-helper type 2 (Th2) cell infiltration and a promising therapeutic target for T-helper type 1(Th1)/Th2 imbalance.

摘要

背景

含伴侣蛋白的TCP1亚基8(CCT8)已被证明与某些癌症的发生和发展有关。然而,尚无研究以泛癌方式报道CCT8的潜在作用。

方法

使用TIMER2.0、GEPIA2、UALCAN和Sangerbox来探究CCT8的表达、预后和甲基化情况。我们使用cBioPortal、TISIDB、SangerBox、TIMER2.0和TISMO来研究CCT8的基因改变以及CCT8与分子亚型、免疫亚型、免疫浸润和免疫治疗反应的关系。通过GEPIA和STRING筛选出CCT8相关基因,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。进行CCK-8、集落形成实验、伤口愈合实验和Transwell实验,以探究CCT8对增殖和迁移的影响。

结果

CCT8在大多数预后不良的癌症中高表达。CCT8的表达水平受启动子区域甲基化和基因改变的影响,与癌症的分子和免疫亚型有关。有趣的是,CCT8与活化的CD4 T细胞和2型辅助性T细胞呈正相关。CCT8在癌症的细胞周期和RNA转运中起重要作用,敲低CCT8可显著抑制肺腺癌细胞的增殖和迁移。

结论

CCT8在促进多种癌症的增殖和迁移中发挥不可或缺的作用。CCT8可能是2型辅助性T(Th2)细胞浸润的生物标志物,也是1型辅助性T(Th1)/Th2失衡的有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5471/10238552/2b8c01b70f0b/JIR-16-2297-g0001.jpg

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