Xiong Si, Peng Huiyong, Ding Xiangmei, Wang Xuehua, Wang Li, Wu Chenguang, Wang Shengjun, Xu Huaxi, Liu Yingzhao
Department of Endocrinology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China.
Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China.
Mol Ther Nucleic Acids. 2019 Sep 6;17:38-48. doi: 10.1016/j.omtn.2019.05.004. Epub 2019 May 22.
Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs), but the role of circRNAs in Hashimoto's thyroiditis (HT) has not been defined. In this study, peripheral blood samples from five patients with HT and five healthy volunteers were investigated by Illumina HiSeq Sequencer. A total of 627 differentially expressed circRNAs including 370 upregulated and 257 downregulated ones were identified in HT patients. Four upregulated circRNAs indicated the same rising tendency toward sequencing results. The expression of hsa_circ_0089172 was upregulated and correlated positively with the serum level of the thyroid peroxidase antibody. Two perfectly matched binding sites of miR-125a-3p were found in hsa_circ_0089172 sequences with bioinformatics tools. The expression of miR-125a-3p was decreased in the HT patients and correlated inversely with an elevated level of hsa_circ_0089172. Moreover, knockdown of hsa_circ_0089172 resulted in an increase of the expression of miR-125a-3p in vitro. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0089172 had significant value in HT diagnosis. Taken together, these results demonstrate that hsa_circ_0089172 as a potential diagnostic biomarker of HT and may play a crucial role in the pathogenesis of HT via sponging miR-125a-3p.
环状RNA(circRNA)是一类新型的非编码RNA分子,通过海绵吸附微小RNA(miRNA)参与多种人类疾病的发生发展,但circRNA在桥本甲状腺炎(HT)中的作用尚未明确。在本研究中,利用Illumina HiSeq测序仪对5例HT患者和5名健康志愿者的外周血样本进行了研究。在HT患者中总共鉴定出627个差异表达的circRNA,其中370个上调,257个下调。4个上调的circRNA在测序结果中呈现相同的上升趋势。hsa_circ_0089172的表达上调,且与甲状腺过氧化物酶抗体的血清水平呈正相关。利用生物信息学工具在hsa_circ_0089172序列中发现了两个与miR-125a-3p完全匹配的结合位点。HT患者中miR-125a-3p的表达降低,且与hsa_circ_0089172水平升高呈负相关。此外,体外敲低hsa_circ_0089172导致miR-125a-3p的表达增加。受试者工作特征(ROC)曲线分析表明,hsa_circ_0089172在HT诊断中具有重要价值。综上所述,这些结果表明hsa_circ_0089172作为HT的潜在诊断生物标志物,可能通过海绵吸附miR-125a-3p在HT的发病机制中发挥关键作用。