Data set fromthe article Voellenkle C, Perfetti A, Carrara M, Fuschi P, Renna LV, Longo M, Sain SB, Cardani R, Valaperta R, Silvestri G, Legnini I, Bozzoni I, Furling D, Gaetano C, Falcone G, Meola G, Martelli F. Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1. Int J Mol Sci. 2019 Apr 19;20(8):1938. doi: 10.3390/ijms20081938. PMID: 31010208; PMCID: PMC6515344.

Data set from the article Voellenkle C, Perfetti A, Carrara M, Fuschi P, Renna LV, Longo M, Sain SB, Cardani R, Valaperta R, Silvestri G, Legnini I, Bozzoni I, Furling D, Gaetano C, Falcone G, Meola G, Martelli F. Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1. Int J Mol Sci. 2019 Apr 19;20(8):1938. doi: 10.3390/ijms20081938. PMID: 31010208; PMCID: PMC6515344.

This is the abstract:

Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by "back-splicing", which is the linking covalently of 3'- and 5'-ends of exons. Thus, circRNA levels might be deregulated in conditions associated with altered RNA-splicing. Significantly, growing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG repeats in the DMPK gene which results in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of nine tested, four transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03, and ZNF609. Their circular fraction values correlated with skeletal muscle strength and with splicing biomarkers of disease severity, and displayed higher values in more severely affected patients. Moreover, Receiver-Operating-Characteristics curves of these four circRNAs discriminated DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and the plasma of DM1 patients, but they were not regulated significantly. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients. In conclusion, this pilot study identified circRNA dysregulation in DM1 patients.

本数据集来自Voellenkle C、Perfetti A、Carrara M、Fuschi P、Renna LV、Longo M、Sain SB、Cardani R、Valaperta R、Silvestri G、Legnini I、Bozzoni I、Furling D、Gaetano C、Falcone G、Meola G、Martelli F共同发表于《International Journal of Molecular Sciences》的研究论文《Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1》。该论文于2019年4月19日在线发表，刊载于第20卷第8期，页码1938，DOI为10.3390/ijms20081938，PMID为31010208，PMCID为PMC6515344。

以下为该研究的摘要：
环状RNA（circular RNAs, circRNAs）是近年重新被发现的一类非编码RNA，可作为微小RNA（microRNAs, miRNAs）和蛋白质的海绵，参与调控RNA剪接与转录过程。环状RNA通过“反向剪接（back-splicing）”生成，即外显子的3'端与5'端发生共价连接。因此，在RNA剪接异常的病理状态下，环状RNA的表达水平可能出现失调。越来越多的研究证据表明，环状RNA在人类疾病中发挥关键调控作用。
具体而言，1型肌强直性营养不良（myotonic dystrophy type 1, DM1）是一种多系统紊乱疾病，由DMPK基因中扩增的CTG重复序列引发，可导致mRNA剪接异常。本研究通过分析RNA测序（RNA-sequencing）数据集并结合实时定量PCR（quantitative real-time PCR, qPCR）验证，鉴定了DM1患者骨骼肌中表达的环状RNA。在9份检测的肌肉活检样本中，4个转录本的环状RNA比例显著升高：CDYL、HIPK3、RTN4_03及ZNF609。
上述4种环状RNA的环状比例与骨骼肌力量及反映疾病严重程度的剪接生物标志物呈显著正相关，且在病情更严重的患者中数值更高。此外，它们的受试者工作特征曲线（Receiver-Operating-Characteristics curves）可有效区分DM1患者与健康对照个体。
本研究还发现，上述鉴定的环状RNA在DM1患者的外周血单核细胞（peripheral blood mononuclear cells, PBMCs）及血浆中均可被检测到，但表达水平未出现显著调控变化。最后，在源自DM1患者的分化肌源性细胞系中，同样观察到RTN4_03与ZNF609的环状比例升高。
综上，本初步研究证实了DM1患者体内存在环状RNA表达失调的现象。