Findings suggest that NEAT1 and SNHG17, which have been reported to regulate inflammatory responses in multiple pathological conditions, may play important roles in the host response to L. donovani infection and could serve as potential targets for the prevention and treatment of leishmaniasis.
Abstract
Leishmaniasis is a systemic zoonotic disease caused by Leishmania and can be fatal if left untreated. Recent evidence has shown that long non-coding RNAs (lncRNAs) play a crucial role in regulating the immune response to resist microbial infections. In this study, RNA-seq was performed to analyze the transcriptomic profiles of raw264.7 cells infected with Leishmania donovani ( L. donovani ) for 7.5 hours. A total of 50 differentially expressed (DE) lncRNAs and 287 DE mRNAs were identified, revealing the expression characteristics of lncRNAs in raw264.7 cells following L. donovani infection. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the predicted potentially associated genes of these lncRNAs were primarily enriched in pathways associated with host immune responses. Notably, NEAT1 and SNHG17, which have been reported to regulate inflammatory responses in multiple pathological conditions, were among the identified DE lncRNAs. These findings suggest that they may play important roles in the host response to L. donovani infection and could serve as potential targets for the prevention and treatment of leishmaniasis.
It is demonstrated that lncRNA50877 disrupts mitochondrial homeostasis by negatively regulating KRT8 expression, thereby modulating ROS levels, apoptosis, and autophagy; promoting oxidative stress-induced cell injury; and providing favorable conditions for GCRV replication.
Yexuan Zhang, Shuai Liu, Zhiwei Sun et al.· Developmental and Comparativ...· 0 citations
BACKGROUND Non-coding RNAs (ncRNAs) have been shown to play essential roles in various human diseases, including pulmonary tuberculosis (TB). This study aims to investigate differentially expressed ncRNAs, explore their potential biological functions, and determine whether they can serve as biomarkers and therapeutic targets in TB. METHODS Whole-transcriptome RNA sequencing was performed on blood samples from TB patients and healthy controls (n = 3 per group). Differentially expressed mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A competing endogenous RNA (ceRNA) network was constructed, and hub genes were identified via protein–protein interaction network analysis using Cytoscape. RESULTS A total of 507 differentially expressed mRNAs, 107 differentially expressed lncRNAs, 253 differentially expressed circRNAs, and 38 differentially expressed miRNAs were identified. Functional enrichment revealed involvement in pathways related to cellular processes, mTOR signalling, and endocytosis. A circRNA–miRNA–mRNA ceRNA network was constructed, and hub mRNAs including RACK1, EIF3G, and RPS15 were identified. CONCLUSION It is suggested that differentially expressed ncRNAs may play a role in the pathogenesis of TB. The circRNA (hsa_circ_0003340) and the hub mRNA (RACK1) are potential candidates for further exploration as biomarkers for TB infection. Moreover, the ceRNA network constructed in this study may provide new insights into the regulatory mechanisms of TB.
M. Liu, Y.-L. Guo, D.-J. Wu et al.· Public Health Action· 0 citations
Despite 36,000 long non-coding RNAs (lncRNAs) annotated in the human genome, functional characterization remains limited, and the roles of lncRNAs in the interferon (IFN) response are largely unknown. We previously identified VILMIR as an IFN-stimulated lncRNA that enhances the host IFN response. Through analysis of public bulk RNA-seq datasets, we identified two additional lncRNAs that are consistently upregulated following H1N1 influenza infection and interferon-β (IFN-β) treatment. This study aims to identify immune genes that are perturbed by candidate lncRNA knockdowns (KDs) and explore the relationship between KD efficiency of lncRNA-targeting guide RNAs and the scale of transcriptomic perturbations.
To investigate the roles of these lncRNAs, we used CRISPRi to generate stable KD cell lines in human lung epithelial cells, monocytes, and T-lymphoblasts. These cell lines were treated with IFN-β for 6 hours, and mock versus IFN-treated samples were analyzed using 10x CRISPRi scRNA-seq analysis.
Transcriptome analysis of each lncRNA KD line compared to controls revealed a set of differentially expressed immune genes in response to IFN-β stimulation.
In summary, we have identified two novel interferon-responsive human lncRNAs that may play important roles in the regulation of the host interferon response across different cell types. The results provide mechanistic targets for future studies and serve as preliminary data for future large-scale screens of candidate lncRNAs.
National Institutes of Health Grant R21AI147187
Immune Response Regulation: Molecular Mechanisms (IRM)
Alexandra Istishin, Kristen John, Ethan Smith et al.· Journal of Immunology· 0 citations
Nervous necrosis virus (NNV) is a major viral pathogen that causes viral nervous necrosis in a wide range of fish species and poses a serious threat to global aquaculture. However, the antiviral responses of mandarin fish (Siniperca chuatsi) to NNV infection remain poorly understood. In this study, we investigated host antiviral responses using Chinese perch brain (CPB) cell line and in vivo infection models. Transcriptome sequencing of red-spotted grouper nervous necrosis virus (RGNNV)-infected CPB cells revealed extensive transcriptional reprogramming, with numerous interferon-stimulated genes (ISGs) significantly upregulated. Comparative transcriptomic analysis across multiple teleost species identified a conserved set of ISGs induced during RGNNV infection, including CMPK2, RSAD2, DHX58, IRF3, and EPSTI1. Among these genes, CMPK2 showed strong induction in both infected CPB cells and mandarin fish brain tissues. Functional assays further demonstrated that CMPK2 overexpression significantly inhibited RGNNV replication in CPB cells and was accompanied by increased expression of several interferon-related genes. These findings provide the first functional evidence that CMPK2 restricts RGNNV infection in S. chuatsi. Our study highlights a conserved interferon-responsive antiviral module in teleost fish and identifies CMPK2 as a potential antiviral effector involved in host defense against RGNNV infection.
Chanxia Qin, Jinlong Huang, Linmiao Li et al.· Developmental and Comparativ...· 0 citations
ENST00000615487.1 is a structurally stable lncRNA exhibiting context-dependent expression and localization patterns in CRC, suggesting a potential shift from nuclear transcriptional regulation toward cytoplasmic post-transcriptional functions during colorectal carcinogenesis.
Nataša Đokić, Anastasija Bubanja, Jelena Karanović et al.· Non-Coding RNA· 0 citations
Glaesserella parasuis (G. parasuis) is a major respiratory pathogen in piglets, but the regulatory mechanisms underlying its induced pulmonary inflammation remain poorly understood. In this study, whole-transcriptome sequencing was carried out on lung tissues from colostrum-deprived piglets with mild and severe serotype 5 G. parasuis infection and healthy controls. Differential expression (DE) analysis revealed 299 nominally DE mRNAs and 408 nominally DE lncRNAs in the mild group, increasing to 625 and 1193, respectively, in the severe group. Ingenuity Pathway Analysis identified the S100 family signaling pathway as a core inflammatory module predicted to be activated across both infection grades, with its transcriptional involvement expanding from 8 genes in mild infection to 42 genes in severe infection. Notably, G-protein-coupled receptors (GPCRs) accounted for nearly half (19/42) of the S100-associated DE genes in severe infection, covering multiple functional categories including chemokine receptors, lipid mediator receptors, and metabotropic receptors, suggesting systemic activation of the GPCR family in severe inflammation. Weighted gene co-expression network analysis identified multiple lncRNA candidates, among which two—LOC110256217 and LOC110259349—showed severity-associated connectivity patterns and were selected for further validation. Following G. parasuis infection, time-series RT-qPCR in 3D4/21 cells confirmed their co-expression with corresponding mRNAs and revealed distinct temporal patterns, suggesting their potential differential involvement at early and late stages of the inflammatory response. Collectively, these findings identify a putative lncRNA-S100-GPCR-associated inflammatory module linked to pulmonary inflammation in G. parasuis infection, providing a transcriptomic resource and candidate lncRNA-mRNA pairs for further functional studies and investigation into host resilience. Given the limited sample size (n = 3 per group), these findings should be considered exploratory and warrant validation in larger cohorts.
Jiayi Zeng, Xinqi Zeng, Xiangwei Deng et al.· Animals· 0 citations