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癌症干细胞特异性表达谱揭示了新的膀胱癌生物标志物,并鉴定出 circRNA_103809 是膀胱癌的一个重要调控因子。

Cancer stem cell-specific expression profiles reveal emerging bladder cancer biomarkers and identify circRNA_103809 as an important regulator in bladder cancer.

机构信息

Department of Urology, The 3rd Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China.

Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Aging (Albany NY). 2020 Feb 17;12(4):3354-3370. doi: 10.18632/aging.102816.

Abstract

Bladder cancer stem cells (BCSCs), exhibiting self-renewal and differentiation capacities, may contribute to the tumor initiation, metastasis, recurrence and drug resistance of bladder cancer. However, the underlying functional mechanisms of BCSCs remain to be clarified. In this study, we describe the differentially-expressed mRNAs, lncRNAs, and circRNAs in BCSCs compared with that in bladder cancer non-stem cells (BCNSCs) through the transcriptome microarray data analysis using bladder cancer patients' specimens. CircRNA_103809, the top one among the highly expressed circRNA identified in BCSCs, promotes the self-renewal, migration and invasion capabilities of bladder cancer by acting as a miR-511 sponge. Additionally, GO and KEGG pathway analysis suggest the differentially expressed genes identified may be involved in the cellular metabolism, differentiation and metastasis regulation of the cancer cells. Co-expression networks of lncRNAs/mRNAs and circRNAs/mRNAs constructed by WGCNA give a picture of the non-coding/coding RNAs regulating patterns in BCSCs. Notably, as core genes in the networks, AHCY, C6orf136 and LRIG1 show high potential to be prognosticators for bladder cancer. Therefore, further studies of non-coding RNA functional mechanisms in BCSCs is valuable for detecting the pathogenic mechanisms and discovering novel biomarkers in bladder cancer.

摘要

膀胱癌干细胞(BCSCs)具有自我更新和分化能力,可能有助于膀胱癌的肿瘤起始、转移、复发和耐药性。然而,BCSCs 的潜在功能机制仍需阐明。在这项研究中,我们通过对膀胱癌患者标本的转录组微阵列数据分析,描述了与膀胱癌非干细胞(BCNSCs)相比,BCSCs 中差异表达的 mRNA、lncRNA 和 circRNA。在 BCSCs 中鉴定的高度表达的 circRNA 中排名第一的 circRNA_103809,通过充当 miR-511 的海绵,促进了膀胱癌的自我更新、迁移和侵袭能力。此外,GO 和 KEGG 通路分析表明,鉴定的差异表达基因可能参与了癌细胞的细胞代谢、分化和转移调节。WGCNA 构建的 lncRNA/mRNA 和 circRNA/mRNA 共表达网络描绘了 BCSCs 中调节非编码/编码 RNA 的模式。值得注意的是,作为网络中的核心基因,AHCY、C6orf136 和 LRIG1 具有成为膀胱癌预后标志物的高潜力。因此,对 BCSCs 中非编码 RNA 功能机制的进一步研究对于检测膀胱癌的发病机制和发现新的生物标志物具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ce8/7066924/7e202bfa9160/aging-12-102816-g001.jpg

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