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调控睾丸生殖细胞肿瘤通过上皮-间充质转化和免疫途径的转移。

regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways.

机构信息

Department of Urology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China.

出版信息

Bioengineered. 2022 May;13(5):12141-12155. doi: 10.1080/21655979.2022.2073128.

Abstract

Testicular germ cell tumor (TGCT) is a relatively rare entity tumor, accounting for only 1% of all male cancers. However, it is the most common solid tumor in young men between 15 and 34 years old. Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the functions of lncRNAs in TGCT have only rarely been investigated. LncRNAs associated with TGCT were identified using Gene Expression Omnibus (GEO) database and UCSC XENA database data mining. The effects of on NCCIT cell migration and invasion were evaluated in transwell assays. The expression levels of epithelial-mesenchyme transition (EMT)-related proteins in cells knockdown of were analyzed by Western blot. Correlation analyses between lncRNA expression and copy number variation (CNV) and immune cell infiltration were carried out using The Cancer Genome Atl as (TCGA) data. The effect of Panobinostatin targeting in TGCT cells was investigated. We observed higher expression in TGCT. The migratory and invasive properties of TGCT cells were augmented by , likely via its effects on modulating the expression of epithelial-mesenchyme transition (EMT) related proteins: CTNNB1, ZEB1, CDH2, Snail and VIM. Moreover, expression and CNV correlated negatively with the infiltration of immune cells. In addition, Panobinostat might be a possible candidate drug to target in TGCT. performs important pro-migration and invasion functions in the pathogenesis of TGCT. could be used as diagnostic, prognostic, immune marker and therapeutic target to develop effective treatment of TGCT.

摘要

睾丸生殖细胞肿瘤 (TGCT) 是一种相对罕见的实体肿瘤,仅占所有男性癌症的 1%。然而,它是 15 至 34 岁年轻男性中最常见的实体肿瘤。长链非编码 RNA (lncRNA) 参与各种生理和病理过程。然而,lncRNA 在 TGCT 中的功能很少被研究过。使用基因表达综合 (GEO) 数据库和 UCSC XENA 数据库数据挖掘鉴定与 TGCT 相关的 lncRNA。通过 Transwell 分析评估 lncRNA 对 NCCIT 细胞迁移和侵袭的影响。通过 Western blot 分析细胞中 EMT 相关蛋白的表达水平。使用癌症基因组图谱 (TCGA) 数据进行 lncRNA 表达和拷贝数变异 (CNV) 与免疫细胞浸润之间的相关性分析。研究了靶向 lncRNA 的 Panobinostat 在 TGCT 细胞中的作用。我们观察到 TGCT 中表达水平较高。通过靶向 lncRNA 可能通过调节上皮-间充质转化 (EMT) 相关蛋白的表达来增强 TGCT 细胞的迁移和侵袭特性:CTNNB1、ZEB1、CDH2、Snail 和 VIM。此外,表达和 CNV 与免疫细胞浸润呈负相关。此外,Panobinostat 可能是靶向 TGCT 的候选药物。在 TGCT 的发病机制中,起着重要的促迁移和侵袭作用。可作为诊断、预后、免疫标志物和治疗靶点,为开发有效的 TGCT 治疗方法提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f3e/9275957/08a2a77ca326/KBIE_A_2073128_UF0001_OC.jpg

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