Xu Wenxin, Liu Shuangchun, Li Wanqian, Xu Bin, Shan Ting, Lin Ronghai, Du Yun-Ting, Chen Guang
Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital), School of Medicine, Taizhou University, No 1139 shifu road, Taizhou, Jiaojiang district 318000, China.
Graduate school, Jiamusi University, No 148 xuefu street, Jiamusi Xiangyang district 154007, China.
ACS Infect Dis. 2025 Apr 11;11(4):1018-1029. doi: 10.1021/acsinfecdis.5c00037. Epub 2025 Mar 14.
The integration of RNA- and DNA-based assays enables the investigation of disease dynamics, specifically assessing the role of asymptomatic or subclinical infections in malaria transmission. Circular RNAs (circRNAs), a distinct category of noncoding RNAs, are implicated in numerous pathogenic mechanisms. As of now, research has yet to explore circRNAs' function in malaria infection. The findings revealed that infection upregulated 60 circRNAs and downregulated 71 in BALB/c mice. We selected 11 differentially expressed (DE) circRNAs according to function prediction of target miRNA-mRNA and coding protein, and these were further confirmed by validation experiments. IRESfinder, GO, and KEGG evaluations indicated that 7 DE circRNAs possess protein-coding potential and are enriched in the MAPK signaling cascade. In 17XL-infected BALB/c mouse models, the findings substantiated that the dynamic characteristics of DE circRNAs correlated with inflammation, and the MAPK and NF-κB signaling cascades were activated, also contributing to the inflammatory reaction during malaria infection. This study establishes -induced circRNA expression as a novel mechanism by which the parasite modulates host immune signaling, advancing the understanding of host cell interactions. In addition, 42 circRNAs were found in normal BALB/c mice, and 25 circRNAs were discovered in 17XL-infected BALB/c mice, excluding 1238 circRNAs shared by normal and 17XL-infected BALB/c mice. infection changes the expression profile of circRNAs in the host, and these altered circRNAs are involved in the inflammatory response during malaria infection. In addition, possibly regulates the reverse splicing of pre-mRNA or m6A modification of RNA, inducing the production of novel circRNAs in the host.
基于RNA和DNA的检测方法相结合，能够对疾病动态进行研究，特别是评估无症状或亚临床感染在疟疾传播中的作用。环状RNA（circRNAs）是一类独特的非编码RNA，与多种致病机制有关。截至目前，尚未有研究探索circRNAs在疟疾感染中的功能。研究结果显示，感染使BALB/c小鼠体内60种circRNAs表达上调，71种circRNAs表达下调。我们根据靶标miRNA-mRNA和编码蛋白的功能预测，筛选出11种差异表达（DE）circRNAs，并通过验证实验进一步证实。IRESfinder、GO和KEGG评估表明，7种DE circRNAs具有蛋白质编码潜力，且在MAPK信号级联中富集。在感染17XL的BALB/c小鼠模型中，研究结果证实DE circRNAs的动态特征与炎症相关，MAPK和NF-κB信号级联被激活，这也促成了疟疾感染期间的炎症反应。本研究确定疟原虫诱导的circRNA表达是寄生虫调节宿主免疫信号的一种新机制，增进了对宿主细胞相互作用的理解。此外，在正常BALB/c小鼠中发现了42种circRNAs，在感染17XL的BALB/c小鼠中发现了25种circRNAs，排除正常和感染17XL的BALB/c小鼠共有的1238种circRNAs。疟原虫感染改变了宿主中circRNAs的表达谱，这些改变的circRNAs参与了疟疾感染期间的炎症反应。此外，疟原虫可能调节前体mRNA的反向剪接或RNA的m6A修饰，诱导宿主中产生新的circRNAs。
