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 LINC00313 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 LINC00313 were analyzed by Western blot. Correlation analyses between lncRNA LINC00313 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 LINC00313 in TGCT cells was investigated. We observed higher LINC00313 expression in TGCT. The migratory and invasive properties of TGCT cells were augmented by LINC00313, likely via its effects on modulating the expression of epithelial-mesenchyme transition (EMT) related proteins: CTNNB1, ZEB1, CDH2, Snail and VIM. Moreover, LINC00313 expression and CNV correlated negatively with the infiltration of immune cells. In addition, Panobinostat might be a possible candidate drug to target LINC00313 in TGCT. LINC00313 performs important pro-migration and invasion functions in the pathogenesis of TGCT. LINC00313 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岁的年轻男性中最常见的实体瘤。长链非编码RNA(lncRNAs)参与各种生理和病理过程。然而,lncRNAs在TGCT中的功能很少被研究。使用基因表达综合(GEO)数据库和UCSCXENA数据库数据挖掘鉴定与TGCT相关的LncRNA。在transwell测定中评估LINC00313对NCCIT细胞迁移和侵袭的影响。通过Westernblot分析LINC00313敲低细胞中上皮-间质转化(EMT)相关蛋白的表达水平。使用癌症基因组Atl作为(TCGA)数据进行lncRNALINC00313表达与拷贝数变异(CNV)和免疫细胞浸润之间的相关性分析。研究了TGCT细胞中靶向LINC00313的Panobinostatin的作用。我们在TGCT中观察到更高的LINC00313表达。LINC00313增强了TGCT细胞的迁移和侵袭特性,可能是通过其对调节上皮间质转化(EMT)相关蛋白CTNNB1,ZEB1,CDH2,Snail和VIM表达的影响。此外,LINC00313表达和CNV与免疫细胞浸润呈负相关。此外,帕比司他可能是TGCT中靶向LINC00313的候选药物。LINC00313在TGCT的发病机制中具有重要的促迁移和侵袭功能。LINC00313可以用作诊断,预后,免疫标志物和治疗靶点,以开发TGCT的有效治疗方法。