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甲基化激活的癌症睾丸基因 SPANXC 促进肺腺癌中的细胞转移。

Hypomethylation-activated cancer-testis gene SPANXC promotes cell metastasis in lung adenocarcinoma.

机构信息

Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

出版信息

J Cell Mol Med. 2019 Nov;23(11):7261-7267. doi: 10.1111/jcmm.14532. Epub 2019 Sep 4.

DOI:10.1111/jcmm.14532
PMID:31483565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6815806/
Abstract

Many studies have shown that there were similarity between tumorigenesis and gametogenesis. Our previous work found that cancer-testis (CT) genes could serve as a novel source of candidate of cancer. Here, by analysing The Cancer Genome Atlas (TCGA) database, we characterized a CT gene, SPANXC, which is expressed only in testis. The SPANXC was reactivated in lung adenocarcinoma (LUAD) tissues. And the expression of SPANXC was associated with prognosis of LUAD. We also found that the activation of SPANXC was due to the promoter hypomethylation of SPANXC. Moreover, SPANXC could modulate cell metastasis both in vitro and in vivo. Mechanistically, we found that SPANXC could bind to ROCK1, a metastasis-related gene, and thus SPANXC may regulate cell metastasis partly through interaction with ROCK1 in LUAD. Together, our results demonstrated that the CT expression pattern of SPANXC served as a crucial role in metastasis of LUAD. And these data further corroborated the resemblance between processes of germ cell development and tumorigenesis, including migration and invasion.

摘要

许多研究表明肿瘤发生和配子发生之间存在相似性。我们之前的工作发现,癌症睾丸(CT)基因可以作为癌症候选物的新来源。在这里,通过分析癌症基因组图谱(TCGA)数据库,我们鉴定了一个仅在睾丸中表达的 CT 基因 SPANXC。SPANXC 在肺腺癌(LUAD)组织中被重新激活。并且 SPANXC 的表达与 LUAD 的预后相关。我们还发现 SPANXC 的激活是由于 SPANXC 启动子的低甲基化。此外,SPANXC 可以在体外和体内调节细胞转移。在机制上,我们发现 SPANXC 可以与 ROCK1 结合,ROCK1 是一个与转移相关的基因,因此 SPANXC 可能通过与 LUAD 中的 ROCK1 相互作用部分调节细胞转移。总之,我们的结果表明,SPANXC 的 CT 表达模式在 LUAD 的转移中起着关键作用。这些数据进一步证实了生殖细胞发育和肿瘤发生过程之间的相似性,包括迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/e2c991a40594/JCMM-23-7261-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/1a7a6095985b/JCMM-23-7261-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/18185d4bc6fb/JCMM-23-7261-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/9bb1167dce8f/JCMM-23-7261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/af321e608fd1/JCMM-23-7261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/e2c991a40594/JCMM-23-7261-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/1a7a6095985b/JCMM-23-7261-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/18185d4bc6fb/JCMM-23-7261-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/9bb1167dce8f/JCMM-23-7261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/af321e608fd1/JCMM-23-7261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dab/6815806/e2c991a40594/JCMM-23-7261-g005.jpg

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本文引用的文献

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Oncogene. 2019 Mar;38(10):1611-1624. doi: 10.1038/s41388-018-0548-x. Epub 2018 Oct 23.
2
A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1.一种新型长链非编码 RNA HOXC-AS3 通过与 YBX1 结合介导胃癌的肿瘤发生。
Genome Biol. 2018 Oct 4;19(1):154. doi: 10.1186/s13059-018-1523-0.
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Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
全球癌症统计数据 2018:GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
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Systematic identification of long non-coding RNAs with cancer-testis expression patterns in 14 cancer types.在14种癌症类型中对具有癌-睾丸表达模式的长链非编码RNA进行系统鉴定。
Oncotarget. 2017 Oct 19;8(55):94769-94779. doi: 10.18632/oncotarget.21930. eCollection 2017 Nov 7.
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Cancer/Testis Antigens: "Smart" Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers.癌/睾丸抗原:用于前列腺癌及其他癌症诊断和预后的“智能”生物标志物。
Int J Mol Sci. 2017 Mar 31;18(4):740. doi: 10.3390/ijms18040740.
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