Ning Qiu-Yue, Liu Na, Wu Ji-Zhou, Hu Die-Fei, Wei Qi, Zhou Jin-Ai, Zou Jun, Zang Ning, Li Guo-Jian
Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Infect Drug Resist. 2021 Nov 25;14:4931-4948. doi: 10.2147/IDR.S338321. eCollection 2021.
In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection.
We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs.
A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥1 and FDR <0.01) in the two groups. A validation analysis revealed that three miRNAs (miR-192-5p, miR-194-5p and miR-1246) were upregulated in exosomes from AIDS combined with TM infection patients. ROC analyses showed that the AUC in combined diagnosis of the three miRNAs was 0.742, and the diagnostic sensitivity and specificity were 0.568 and 0.861, respectively. In the biological process analysis, all the 3 miRNAs were involved in transcription, DNA-templated and positive regulation of transcription from RNA polymerase II promoter. At the same time, the related pathways were involved in TGF-β signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc.
miR-192-5p, miR-194-5p and miR-1246 in serum exosomes might be a potential biomarker for AIDS combined with TM infection patients, which may be involved in TGF-β signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. Further research is needed on the biological functions and mechanisms of these miRNAs.
为了寻找艾滋病合并毛滴虫（TM）感染的早期诊断标志物，我们检测并分析了有或没有TM感染的艾滋病患者血清外泌体中的微小RNA（miRNA）。
我们通过RNA测序分析了17例未合并TM感染的艾滋病患者和15例合并TM感染的艾滋病患者混合样本血清外泌体中miRNA的表达水平。为进行外部验证，我们在一个独立队列中使用实时定量聚合酶链反应（qRT-PCR）对35例未合并TM感染的艾滋病患者和33例合并TM感染的艾滋病患者进行验证。最后，利用生物信息学预测有意义的miRNA的靶基因和通路。
两组中共有131种血清外泌体miRNA差异表达（log2FC≥1且FDR<0.01），其中73种上调，59种下调。验证分析显示，合并TM感染的艾滋病患者外泌体中有三种miRNA（miR-192-5p、miR-194-5p和miR-1246）上调。ROC分析显示，这三种miRNA联合诊断的AUC为0.742，诊断敏感性和特异性分别为0.568和0.861。在生物学过程分析中，所有这三种miRNA均参与转录、DNA模板化以及RNA聚合酶II启动子转录的正调控。同时，相关通路涉及转化生长因子-β（TGF-β）信号通路、腺苷酸活化蛋白激酶（AMPK）信号通路、Wnt信号通路、丝裂原活化蛋白激酶（MAPK）信号通路、环磷酸鸟苷-蛋白激酶G（cGMP-PKG）和环磷酸腺苷（cAMP）信号通路等。
血清外泌体中的miR-192-5p、miR-194-5p和miR-1246可能是艾滋病合并TM感染患者的潜在生物标志物，其可能参与TGF-β信号通路、AMPK信号通路、Wnt信号通路、MAPK信号通路、cGMP-PKG和cAMP信号通路等。需要对这些miRNA的生物学功能和机制进行进一步研究。
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