通过构建竞争性内源RNA网络识别潜在的椎间盘疾病相关circRNA

环状RNA(circRNA)可以通过竞争性结合微小RNA(miRNA),从而降低miRNA对其他靶标RNAs的抑制作用,进而间接调控其表达水平。这种竞争性关系代表了一种全新的基因调控机制,在癌症生理和发展中起重要作用。我们运用生物信息学的方法,对基因表达谱、circRNA探针谱重注释处理,并且结合MiRanda算法预测的miRNA靶点信息构建了竞争性内源RNA(ceRNA)网络,发现了五个与疾病相关的重要模块。其中通过hsa-miR-17-3p介导的CD74与hsa_circ_0001320,通过hsa-let-7a-2-3p介导的PAPSS2与hsa_circ_0000077两组ceRNA关系在椎间盘变性中起到重要的分子调控作用,从而成为潜在的临床标志物。进一步地,通过对靶基因的功能注释预测了这两个circRNA的生物学功能,其中明显与椎间盘炎症反应和骨发育相关,为临床基因检测预测疾病和药物靶点治疗提供依据并且也为椎间盘疾病的科学研究提供思路。

Identification of potential intervertebral disc disease-related circRNAs byconstructing competing endogenous RNA networks

CircRNAs can reduce the inhibitory effect of miRNA on other target RNAs and indirectly regulate its expression level by competitive binding of small RNAs to miRNAs. This competitive relationship represents a novel gene regulation mechanism that plays an important role in cancer physiology and development. Using the bioinformatics method, we reannotated the gene expression profile and circRNA probe profile. With the miRNA target information predicted by the MiRanda algorithm,we constructed a competitive endogenous RNAs network and found five important modules related to the disease. The relations of the two ceRNAs, i.e. CD74 and hsacirc0001320 mediated by hsa-miR-17-3p and PAPSS2 and hsa_circ_0000077 mediated by hsa-let-7a-2-3p, play an important role in regulating the degeneration of intervertebral disc and thus become a potential clinical marker. Further, we predicted the biological functions of the two circRNAs by annotating the function of the target gene, which was significantly related to the inflammatory reaction of the intervertebral disc and bone development. It provides basis for clinical gene detection to predict disease and drug target therapy, as well as ideas for scientific research of intervertebral disc disease.