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Integrated analysis of high-throughput sequencing data reveals the key role of LINC00467 in the invasion and metastasis of testicular germ cell tumors
Cell Death Discovery ( IF 7 ) Pub Date : 2021-08-06 , DOI: 10.1038/s41420-021-00588-9
Hao Bo 1, 2 , Fang Zhu 1 , Zhizhong Liu 1, 3 , Qi Deng 1 , Guangmin Liu 1 , Ruixue Li 1 , Wenbing Zhu 1, 2 , Yueqiu Tan 1, 2 , Gang Liu 1, 2 , Jingyu Fan 4 , Liqing Fan 1, 2
Affiliation  

Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the role of lncRNAs in testicular germ cell tumor (TGCT) has been rarely reported. Our purpose is to comprehensively survey the expression and function of lncRNAs in TGCT. In this study, we used RNA sequencing to construct the lncRNA expression profiles of 13 TGCT tissues and 4 paraneoplastic tissues to explore the function of lncRNAs in TGCT. The bioinformatics analysis showed that many lncRNAs are differentially expressed in TGCT. GO and KEGG enrichment analyses revealed that the differentially expressed lncRNAs participated in various biological processes associated with tumorigenesis in cis and trans manners. Further, we found that the expression of LINC00467 was positively correlated with the poor prognosis and pathological grade of TGCT using WGCNA analysis and GEPIA database data mining. In vitro experiments revealed that LNC00467 could promote the migration and invasion of TGCT cells by regulating the expression of AKT3 and influencing total AKT phosphorylation. Further analysis of TCGA data revealed that the expression was negatively correlated with the infiltration of immune cells and the response to PD1 immunotherapy. In summary, this study is the first to construct the expression profile of lncRNAs in TGCT. It is also the first study to identify the metastasis-promoting role of LNC00467, which can be used as a potential predictor of TGCT prognosis and immunotherapeutic response to provide a clinical reference for the treatment and diagnosis of TGCT metastasis.



中文翻译:

高通量测序数据综合分析揭示LINC00467在睾丸生殖细胞肿瘤侵袭转移中的关键作用

长链非编码 RNA (lncRNA) 参与各种生理和病理过程。然而,lncRNAs在睾丸生殖细胞肿瘤(TGCT)中的作用鲜有报道。我们的目的是全面调查lncRNAs在TGCT中的表达和功能。本研究利用RNA测序构建了13个TGCT组织和4个副肿瘤组织的lncRNA表达谱,探讨lncRNAs在TGCT中的功能。生物信息学分析表明,许多lncRNAs在TGCT中差异表达。GO和KEGG富集分析表明,差异表达lncRNAs参加了与肿瘤发生相关的各种生物过程的顺式反式礼仪。此外,我们使用WGCNA分析和GEPIA数据库数据挖掘发现LINC00467的表达与TGCT的不良预后和病理分级呈正相关。体外实验表明,LNC00467可以通过调节AKT3的表达和影响AKT总磷酸化来促进TGCT细胞的迁移和侵袭。TCGA 数据的进一步分析显示,该表达与免疫细胞浸润和对 PD1 免疫治疗的反应呈负相关。总之,本研究首次构建了lncRNAs在TGCT中的表达谱。这也是第一个确定 LNC00467 促进转移作用的研究,

更新日期:2021-08-07
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