circHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150.

circHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150.
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circHLA-C 通过海绵 miR-150 在狼疮性肾炎中发挥重要作用

DOI:
10.1016/j.omtn.2017.12.006
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发表时间:
2018-03-02
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Zhou H
Zhou H
中科院分区:
其他
文献类型:
--
作者:
Luan J;Jiao C;Kong W;Fu J;Qu W;Chen Y;Zhu X;Zeng Y;Guo G;Qi H;Yao L;Pi J;Wang L;Zhou H

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环状RNA(circRNA)通过吸收微小RNA(miRs)参与多种疾病的发病机制。然而,circRNA在肾小球疾病中的作用仍未报道。我们先前报道了miR-150与狼疮性肾炎(LN)患者的肾慢性指数呈正相关。我们的目的是研究LN患者的肾脏circRNA谱以及circRNA和miR-150之间的相互作用。来自患有IV类LN的未经治疗的女性患者的六个肾活检组织和来自泌尿科患者的五个正常肾组织用于circRNA测序。在LN组织中共检测到171个circRNA,与正常对照组相比差异表达2倍。通过实时qPCR验证了10个选择的circRNA,并且7个circRNA显示出与测序结果相同的显著增加。circHLA-C与蛋白尿(R = 0.92,p < 0.01)、血清肌酐(R = 0.76,p = 0.08)、肾活动指数(R = 0.88,p < 0.05)和新月体肾小球(R = 0.93,p < 0.01)呈正相关。与正常对照组相比,LN患者肾circHLA-C升高2.72倍,miR-150降低66%(p < 0.05)。生物信息学分析预测miR-150受circHLA-C调控,并且在circHLA-C和miR-150之间显示出一个完美匹配的种子。LN患者肾脏miR-150与circHLA-C呈负相关趋势。结论:circHLA-C可能通过吞噬miR-150在狼疮性肾炎的发病机制中发挥重要作用。
Circular RNAs (circRNAs) participate in the pathogenesis of various diseases by sponging microRNAs (miRs). However, the roles of circRNAs remain unreported in glomerular diseases. We previously reported that miR-150 positively correlated with renal chronicity index in patients with lupus nephritis (LN). We aimed to investigate renal circRNA profiling and the interaction between circRNAs and miR-150 in LN patients. Six renal biopsies from untreated female patients with LN class IV and five normal kidney tissues from urology patients were used for circRNA sequencing. 171 circRNAs with 2-fold differential expression were identified in LN compared with normal control. Ten selected circRNAs were validated by real-time qPCR, and seven circRNAs showed the same significant increases as the sequencing results. circHLA-C positively correlated with proteinuria (R = 0.92, p < 0.01), serum creatinine (R = 0.76, p = 0.08), renal activity index (R = 0.88, p < 0.05), and crescentic glomeruli (R = 0.93, p < 0.01). Renal circHLA-C increased 2.72-fold, and miR-150 decreased 66% in LN compared with normal control (p < 0.05). Bio-informatic analysis predicted miR-150 was regulated by circHLA-C and displayed one perfect match seed between circHLA-C and miR-150. The renal miR-150 showed a tendency of negative correlation with circHLA-C in LN patients. In conclusion, circHLA-C may play an important role in the pathogenesis of lupus nephritis by sponging miR-150.
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