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长链非编码 RNA 甲基化在膀胱癌患者预后中的作用。

Role of hypermethylated-lncRNAs in the prognosis of bladder cancer patients.

机构信息

Department of Urology, 74573Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen, P.R. China.

出版信息

J Int Med Res. 2021 Oct;49(10):3000605211049946. doi: 10.1177/03000605211049946.

DOI:10.1177/03000605211049946
PMID:34617815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8504649/
Abstract

OBJECTIVE

To explore the hypermethylated long non-coding (lnc)RNAs involved in bladder carcinogenesis and prognosis.

METHODS

Reduced representation bisulfite sequencing and RNA sequencing were performed on five paired tumor and adjacent normal tissue samples from bladder cancer patients. The differentially methylated regions around transcription start sites and differentially expressed genes, including lncRNAs, were analyzed. Correlations between DNA methylation modifications and the expression of lncRNAs were examined. Survival analysis was surveyed on the GEPIA web server.

RESULTS

We identified 19,560 hypomethylated and 68,781 hypermethylated differentially methylated regions around transcription start sites in bladder cancer tissues. In total, 2321 differentially expressed genes were found in bladder tumors, among which, 367 were upregulated and 1954 were downregulated. There were 141 downregulated genes involving eight lncRNAs that were consistently hypermethylated, while 24 upregulated genes were consistently hypomethylated. Survival analysis demonstrated that hypermethylation of lncRNAs LINC00683 and MSC-AS1 were associated with poor overall survival in bladder cancer patients.

CONCLUSION

Some lncRNAs are controlled by DNA methylation in bladder cancer and they might be important factors in bladder carcinogenesis. Hypermethylated lncRNAs including LINC00683 and MSC-AS1 have the potential to be prognostic biomarkers for bladder cancer.

摘要

目的

探索膀胱癌发生和预后相关的异常甲基化长链非编码 RNA(lncRNA)。

方法

对 5 对膀胱癌患者肿瘤组织及其配对的癌旁正常组织进行重亚硫酸盐测序和 RNA 测序,分析差异甲基化区域(DMRs)和差异表达基因(包括 lncRNA)。检测 DNA 甲基化修饰与 lncRNA 表达的相关性。利用 GEPIA 网站进行生存分析。

结果

在膀胱癌组织中,我们共鉴定出 19560 个转录起始位点处的低甲基化 DMR 和 68781 个高甲基化 DMR。在膀胱癌组织中,共发现 2321 个差异表达基因,其中上调基因 367 个,下调基因 1954 个。有 8 个 lncRNA 的 141 个下调基因涉及一致的高甲基化,而 24 个上调基因涉及一致的低甲基化。生存分析表明,lncRNA LINC00683 和 MSC-AS1 的高甲基化与膀胱癌患者的总生存期不良相关。

结论

在膀胱癌中,一些 lncRNA 受 DNA 甲基化调控,可能是膀胱癌发生的重要因素。异常高甲基化的 lncRNA,包括 LINC00683 和 MSC-AS1,可能成为膀胱癌的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/57730d0b159c/10.1177_03000605211049946-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/12913dd3f6c4/10.1177_03000605211049946-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/e1a5dab2f2c2/10.1177_03000605211049946-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/dee656ba1b68/10.1177_03000605211049946-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/4c6cbfc51ff6/10.1177_03000605211049946-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/57730d0b159c/10.1177_03000605211049946-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/12913dd3f6c4/10.1177_03000605211049946-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/e1a5dab2f2c2/10.1177_03000605211049946-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/dee656ba1b68/10.1177_03000605211049946-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/4c6cbfc51ff6/10.1177_03000605211049946-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/8504649/57730d0b159c/10.1177_03000605211049946-fig5.jpg

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本文引用的文献

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LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis.长链非编码 RNA BCRT1 通过靶向 miR-1303/PTBP3 轴促进乳腺癌进展。
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lncRNA MSC-AS1 activates Wnt/β-catenin signaling pathway to modulate cell proliferation and migration in kidney renal clear cell carcinoma via miR-3924/WNT5A.
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