Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Transl Med. 2018 Oct 4;16(1):272. doi: 10.1186/s12967-018-1646-9.
In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19-24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level.
We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein-protein and mRNA-miRNA networks to identify highly regulated miRNA.
In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60-71% and 69-81% respectively and area under curve (AUC) of 0.7 (p < 0.05). Moreover, in silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA-miRNA networks, suggesting their putative role in complicated P. vivax malaria.
miR-7977 might act as a potential biomarker for differentiating complicated P. vivax malaria from uncomplicated type. The elevated levels of miR-7977 may have a role to play in the disease pathology through UBA52 or TGF-beta signalling pathway.
近年来，已报道间日疟原虫可引起与死亡率相关的严重感染。临床评估对早期识别向致命状态发展的患者的准确性有限。研究人员试图确定严重疟疾的血清和血浆标志物。微小 RNA (miRNA) 的发现开创了鉴定各种感染性和非感染性疾病早期生物标志物的时代。微小 RNA (miRNA) 是长度为 19-24nt 的小非编码 RNA 分子，负责在转录后水平调节大多数人类基因的表达。
我们通过微阵列鉴定差异表达的 miRNA，并通过 qRT-PCR 验证所选 miRNA。我们评估了这些上调的 miRNA 对复杂间日疟原虫疟疾的诊断潜力。进一步，进行生物信息学分析以构建蛋白质-蛋白质和 mRNA-miRNA 网络，以鉴定高度调控的 miRNA。
在本研究中，探索了 miRNA 作为复杂间日疟原虫疟疾潜在生物标志物的效用。通过 miRNA 微阵列发现 276 个 miRNA 存在差异表达，其中 5 个 miRNA (hsa-miR-7977、hsa-miR-28-3p、hsa-miR-378-5p、hsa-miR-194-5p 和 hsa-miR-3667-5p) 通过 qRT-PCR 发现明显上调在复杂的间日疟原虫疟疾患者中。这些 5 个 miRNA 的诊断潜力具有显著意义，灵敏度和特异性分别为 60-71%和 69-81%，曲线下面积 (AUC) 为 0.7(p<0.05)。此外，上调 miRNA 的共同靶标的计算分析显示 UBA52 和 hsa-miR-7977 是 PPI 和 mRNA-miRNA 网络中的主要调节枢纽，表明它们在复杂的间日疟原虫疟疾中可能发挥作用。
miR-7977 可能作为区分复杂间日疟原虫疟疾与非复杂型的潜在生物标志物。miR-7977 水平的升高可能通过 UBA52 或 TGF-β信号通路在疾病发病机制中发挥作用。
