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高通量测序数据的综合分析揭示了LINC00467在睾丸生殖细胞肿瘤侵袭和转移中的关键作用。

Integrated analysis of high-throughput sequencing data reveals the key role of LINC00467 in the invasion and metastasis of testicular germ cell tumors.

作者信息

Bo Hao, Zhu Fang, Liu Zhizhong, Deng Qi, Liu Guangmin, Li Ruixue, Zhu Wenbing, Tan Yueqiu, Liu Gang, Fan Jingyu, Fan Liqing

机构信息

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.

Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.

出版信息

Cell Death Discov. 2021 Aug 6;7(1):206. doi: 10.1038/s41420-021-00588-9.

Abstract

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.

摘要

长链非编码RNA(lncRNAs)参与多种生理和病理过程。然而,lncRNAs在睾丸生殖细胞肿瘤(TGCT)中的作用鲜有报道。我们的目的是全面研究lncRNAs在TGCT中的表达及功能。在本研究中,我们使用RNA测序构建了13例TGCT组织和4例癌旁组织的lncRNA表达谱,以探索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富集分析显示,差异表达的lncRNAs以顺式和反式方式参与了与肿瘤发生相关的各种生物学过程。此外,我们通过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可通过调节AKT3的表达并影响总AKT磷酸化来促进TGCT细胞的迁移和侵袭。对TCGA数据的进一步分析显示,该表达与免疫细胞浸润及对PD1免疫治疗的反应呈负相关。总之,本研究首次构建了TGCT中lncRNAs的表达谱。这也是首次鉴定出LNC00467具有促进转移的作用,其可作为TGCT预后和免疫治疗反应的潜在预测指标,为TGCT转移的治疗和诊断提供临床参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/434c/8346510/5fe868a29a10/41420_2021_588_Fig1_HTML.jpg

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