Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.
Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.
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DOI：
10.1038/s41525-017-0038-z
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发表时间：
2017
影响因子：
5.3
通讯作者：
Pedersen JS
中科院分区：
文献类型：
--
作者：
Okholm TLH;Nielsen MM;Hamilton MP;Christensen LL;Vang S;Hedegaard J;Hansen TB;Kjems J;Dyrskjøt L;Pedersen JS
环状RNA（circRNA）在各种癌症类型中的功能和生物标志物潜力是一个新兴的研究领域，因为新出现的证据将circRNA与肿瘤发生联系起来。在这里，我们分析了来自非肌肉浸润性膀胱癌（NMIBC）患者的457个肿瘤中circRNA的表达。我们发现一组高度表达的circRNA具有保守的核心剪接位点，与Alu重复序列相关，并富含同义限制元件以及microRNA靶位点。我们鉴定了113种丰富的circRNA，它们在高风险和低风险肿瘤亚型之间差异表达。对无进展生存期的分析揭示了13种circRNA，其中包括circHIPK3和circCDYL，其表达与独立于线性转录物和宿主基因的进展相关。总之，我们的研究结果表明，丰富的circRNA具有多种生物学特征，将它们与低表达的circRNA和非环化外显子区分开来，并表明circRNA可能作为一类新的NMIBC预后生物标志物。非编码“环状”RNA分子的表达水平可用作早期膀胱癌患者的预后生物标志物。由来自丹麦奥胡斯大学医院的Trine Line豪格Okholm和Jakob Skou Pedersen领导的一个研究小组，分析了457名膀胱癌患者活检肿瘤样本中这些形成环的潜在基因调节RNA的表达，这些患者没有侵犯附近的肌肉组织。他们鉴定了一组113种环状RNA，这些环状RNA在不同分子亚型的膀胱癌患者之间丰富且差异表达。研究人员还发现了一组较小的13种环状RNA，其表达水平与疾病进展相关。这些非编码RNA分子通过指示可能的患者结果，可能作为未来的诊断辅助工具，为治疗策略和决策提供信息。
The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We show that a set of highly expressed circRNAs have conserved core splice sites, are associated with Alu repeats, and enriched with Synonymous Constraint Elements as well as microRNA target sites. We identified 113 abundant circRNAs that are differentially expressed between high and low-risk tumor subtypes. Analysis of progression-free survival revealed 13 circRNAs, among them circHIPK3 and circCDYL, where expression correlated with progression independently of the linear transcript and the host gene. In summary, our results demonstrate that abundant circRNAs possess multiple biological features, distinguishing them from low-expressed circRNAs and non-circularized exons, and suggest that circRNAs might serve as a new class of prognostic biomarkers in NMIBC. Expression levels of non-coding “circular” RNA molecules could be used as a prognostic biomarker for patients with early-stage bladder cancer. A team led by Trine Line Hauge Okholm and Jakob Skou Pedersen from Aarhus University Hospital, Denmark, profiled the expression of these loop-forming, potentially gene-regulating RNAs in biopsied tumor samples from 457 patients with bladder cancer that had not invaded nearby muscle tissue. They identified a suite of 113 circular RNAs that were abundant and differentially expressed between patients with different molecular subtypes of bladder cancer. The researchers also found a smaller set of 13 circular RNAs for which expression levels correlated with disease progression. These non-coding RNA molecules, by indicating likely patient outcomes, could potentially serve as future diagnostic aids to inform treatment strategies and decisions.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
28.5
作者：
Dong Y;He D;Peng Z;Peng W;Shi W;Wang J;Li B;Zhang C;Duan C
通讯作者：
Duan C
影响因子：
16.6
作者：
Hamilton MP;Rajapakshe K;Hartig SM;Reva B;McLellan MD;Kandoth C;Ding L;Zack TI;Gunaratne PH;Wheeler DA;Coarfa C;McGuire SE
通讯作者：
McGuire SE
影响因子：
46.9
作者：
Jeck, William R.;Sharpless, Norman E.
通讯作者：
Sharpless, Norman E.
影响因子：
4.8
作者：
COCQUERELLE, C;MASCREZ, B;BAILLEUL, B
通讯作者：
BAILLEUL, B