Lv Yana, Que Yumei, Su Qiao, Li Qiang, Chen Xi, Lu Haitao
Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, P.R. China.
Innovative Drug Research Centre and School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, P.R. China.
Oncotarget. 2016 Aug 9;7(32):52270-52280. doi: 10.18632/oncotarget.10586.
Aristolochic acid nephropathy (AAN) is a rapidly progressive acute or chronic tubulointerstitial nephritis (TIN). The present study attempted to explore the molecular mechanisms underlying the miRNA-directed development of AAN. Our differentially expressed analysis identified 11 DE-miRNAs and retrieved the target genes of these DE-miRNAs; then, network analysis and functional analysis further identified 6 DE-miRNAs (has-miR-192, has-miR-194, has-miR-542-3p, has-miR-450a, has-miR-584, has-miR-33a) as phenotypic biomarkers of AAN. Surprisingly, of has-miR-192 has been reported to be associated with the pathogenesis of AAN, and has-miR-194, has-miR-542-3p and has-miR-450a was first-time identified to link to the development of AAN. In addition, the expressional changes of has-miR-584 and has-miR-33a may be associated with the development of AAN as well, which must be further confirmed by the associated experiments. Taken together, our work reveals for the first time the regulatory mechanisms of miRNAs in the development of AAN and this will contribute to miRNA-based diagnosis and treatment of AAN.
马兜铃酸肾病（AAN）是一种快速进展的急性或慢性肾小管间质性肾炎（TIN）。本研究试图探索微小RNA（miRNA）介导的AAN发病机制的分子机制。我们的差异表达分析鉴定出11个差异表达的miRNA（DE-miRNA），并检索了这些DE-miRNA的靶基因；然后，网络分析和功能分析进一步确定了6个DE-miRNA（has-miR-192、has-miR-194、has-miR-542-3p、has-miR-450a、has-miR-584、has-miR-33a）作为AAN的表型生物标志物。令人惊讶的是，已有报道称has-miR-192与AAN的发病机制有关，而has-miR-194、has-miR-542-3p和has-miR-450a是首次被鉴定与AAN的发生有关。此外，has-miR-584和has-miR-33a的表达变化可能也与AAN的发生有关，这一点必须通过相关实验进一步证实。综上所述，我们的工作首次揭示了miRNA在AAN发生过程中的调控机制，这将有助于基于miRNA的AAN诊断和治疗。
