BMC GASTROENTEROLOGY
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2024
·Vol. 24
·期 1
·1-10
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IF 2.5
Wen Yuefei,Li Chenyang,Huang Peng,Liu Zhigang,He Yanjun,Liu Bin
Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.
研究领域:
免疫学
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分子生物学
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基因组学
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
·
IF 4.872
Yuhao Wu,Junke Wang,Tianxin Zhao,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro . The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.
研究领域:
生殖生物学
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毒理学
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分子生物学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ocean University of China
·
2024
·Vol. 23
·期 6
·1615-1629
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IF 1.4
Wang Wenwen,Wei Shu,Chen Yadong,Tan Suxu,Shi Kunpeng,Zang Shaoqing,Wang Minmin,Yang Teng,Yang Yingming,Cui Zhongkai,Sha Zhenxia
As an efficient immunostimulant, chitosan oligosaccharide (COS) can enhance the immunity of teleosts; however, the underlying molecular mechanisms still require elucidation. Competing endogenous RNAs (ceRNAs) are vital regulators in the immune response, but their roles in half-smooth tongue sole ( Cynoglossus semilaevis ) remain unclear. In this study, for the first time, we studied whole-transcriptome expression profiles and analyzed ceRNA networks in peripheral blood leukocytes of half-smooth tongue sole treated with COS. A total of 19 circRNAs (DE-circRNAs), 18 miRNAs (DE-miRNAs) and 50 previously identified lncRNAs (DE-lncRNAs) were differentially expressed after COS stimulation. The DE-lncRNAs and DE-miRNAs targeted numerous immunity-related genes, and were enriched in important pathways, including MAPK and Toll-like receptor signaling pathways, suggesting the immunoregulatory roles of COS. Furthermore, we constructed circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks using DE-circRNAs, DE-miRNAs, DE-lncRNAs, and DE-mRNAs. Additionally, a ceRNA network with immunity-related DE-mRNAs was constructed, showing that 3 DE-circRNAs, 12 DE-lncRNAs, and 29 DEGs exhibited crosstalk through 9 DE-miRNAs. Intriguingly, a DE-miRNA in the ceRNA network, miR-144-3p, was targeted by DE-lncRNA tnrc6a , and negatively regulated the genes of inhibitor of nuclear factor kappa B kinases (IKKs) ( ikbkg , ikbkb , and ikbip ) and c3ar1 . Ikbkg , ikbkb , and c3ar1 were significantly up-regulated in macrophages stimulated by LPS. It could be inferred that ncRNAs participated in the immune and inflammatory response by acting as ceRNAs after COS stimulation in teleosts. These findings indicate that COS could enhance the immunity of teleosts by regulating ncRNAs, and lay the foundation for further practical application of COS in aquaculture.
研究领域:
免疫学
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分子生物学
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水产养殖
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转录组学
✓ 已验证
DOI
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
·
IF 3.7
Xiaolan Guo,Kailun Wu,Longrui Dang,Sitong Liu,Jing Xu,Runting Wang,Junyang Xu,Yiming Zhong,Zhao Chen,Buling Wu
Background Pulpitis is an oral disease primarily triggered by microbial infections. Current therapeutic strategies lack specific agents targeting the underlying pathogenic mechanisms. Non-coding RNAs (ncRNAs) and their competitive endogenous RNA (ceRNA) networks have emerged as critical regulators of diverse biological processes, offering novel insights into the pathogenesis of pulpitis and the identification of potential therapeutic targets. Methods RNA sequencing was performed on pulp tissues from healthy individuals and pulpitis patients. Bioinformatics tools were employed to analyse sequencing data, identify differentially expressed messenger RNAs (mRNAs), and construct protein-protein interaction (PPI) networks to pinpoint hub genes. A murine pulpitis model was established to investigate the effects of neutrophil extracellular trap (NET) inhibitors on disease progression. A NET-associated ceRNA regulatory network was systematically constructed based on ceRNA theory. In vitro experiments validated the expression patterns of key ncRNAs and mRNAs in pulpitis. Results Differentially expressed mRNAs, long non-coding RNAs (lncRNAs), and Circular RNAs (circRNAs) were identified in pulpitis. Bioinformatics analysis revealed significant activation of NET-related pathways, with sialic acid-binding immunoglobulin-like lectin-9 (SIGLEC9), complement C3 (C3), H2A clustered histone 14 (H2AC14), and H4 clustered histone 11 (H4C11) identified as core regulatory genes. In vivo experiments demonstrated that NET inhibition alleviated dental pulpitis and necrosis. Furthermore, a novel NET-associated ceRNA regulatory network was established, revealing four critical regulatory axes: LINC00466 / hsa-miR-27a-3p / SIGLEC9, hsa_circDNAH11_003 / hsa-miR-877-5p / C3, hsa_circSLC15A4_001 / hsa-miR-30d-3p / H2AC14, and hsa_circGABBR2_009 / hsa-miR-193b-3p / H4C11. These ncRNAs exhibited significant upregulation in inflamed pulp tissues. Conclusion By constructing a comprehensive NET-associated ceRNA network, we elucidate molecular mechanisms underlying dental pulpitis, providing novel evidence for understanding the disease progression. These findings establish a theoretical foundation for developing targeted therapeutic strategies against pulpitis.
研究领域:
口腔医学
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分子生物学
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免疫学
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生物信息学
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遗传学
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转录组学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AIP Advances
·
2025
·Vol. 15
·期 7
·
IF 1.4
Yu Dong-hua,Wang Yu,Yu Chun-Miao,Zhou Qi,Liu Shu-min,Liu Ting-ting
The aim of this study is to construct a competitive endogenous RNA regulatory network of gouty arthritis through transcriptomics and investigate its underlying pathogenesis. Transcriptomics was performed with the rats’ joints in both the control and model groups. The mRNA, miRNA, lncRNA, and circRNA were analyzed using the R language. The RNA data were visualized as the ceRNA network. Genes were combined, the KEGG pathway was enriched, and the first five pathways were selected. Meanwhile, relationships between genes in the extraction pathway were integrated into a network, and key genes were mapped. mRNA, lncRNA, and circRNA were scored to compare the conservatism of RNA. Finally, lncRNA, circRNA, miRNA, and genes were considered the core, and information about other differential RNAs having a targeted relationship with them (i.e., host genes) was added. Based on ceRNA analysis, the relationship pairs between lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were extracted. A total of 1165 de-mRNAs, 91 de-miRNAs, 456 de-lncRNAs, and 70 de-circRNAs were selected. The key genes were identified for pathway enrichment, such as the phospholipase D signaling pathway and endocytosis. Based on the ceRNA analysis, the networks of lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were constructed. The differentially expressed RNAs between the control and model groups were identified using the transcriptomics of ankle tissue. The findings indicate that mRNA, lncRNA, and circRNA can competitively bind to GA-related miRNAs, leading to mutual regulatory effects. The RNAs identified from the constructed lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks are potential targets for therapeutic drugs and may be involved in the pathogenesis of GA.
研究领域:
分子生物学
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基因组学
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生物信息学
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RNA生物学
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免疫学
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关节炎研究
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Jijin Jiang,Yan Chen,Yue Su,Li Zhang,Hao Qian,Xinmiao Song,Jin-Fu Xu
Background Sepsis is an uncontrolled reaction to infection that causes severe organ dysfunction and is a primary cause of ARDS. Patients suffering both sepsis and ARDS have a poor prognosis and high mortality. However, the mechanisms behind their simultaneous occurrence are unclear. Methods We acquired sepsis and ARDS datasets from GEO and Arrayexpress databases and screened hub genes by WGCNA and machine learning algorithm. For diagnosis and prognosis, ROC curve and survival analysis were used. We performed GO, KEGG, GSEA, immune cell infiltration, drug prediction, molecular docking, transcription factor prediction, and constructed PPI and ceRNA networks to explore these genes and the common mechanisms of sepsis and ARDS. Single-cell data analysis compared immune cell profiles and hub gene localization. Finally, RT-qPCR and H&E staining confirmed the reliability of hub genes using PBMCs samples and mouse models. Results We identified 242 common differentially expressed genes in sepsis and ARDS. WGCNA analysis showed that the turquoise module in GSE95233 is strongly linked to sepsis occurrence and poor prognosis, while the black module in GSE10474 is associated with ARDS. Using WGCNA and three machine learning methods (LASSO, random forest and Boruta), we identified three key genes CX3CR1, PID1 and PTGDS. Models built with them showed high AUC values in ROC curve evaluations and were validated by external datasets, accurately predicting the occurrence and mortality. We further explored the immunological landscape of these genes using immune infiltration and single-cell analysis. Then, the ceRNA, predicted drugs and molecular docking were analyzed. Ultimately, we demonstrated that these genes are expressed differently in human and mouse samples with sepsis and ARDS. Conclusion This study identified three molecular signatures (CX3CR1, PID1 and PTGDS) linked to the diagnosis and poor prognosis of sepsis and ARDS, validated by RT-qPCR and H&E staining in both patient and mouse samples. This research may be valuable for identifying shared biological mechanisms and potential treatment targets for both diseases.
研究领域:
医学遗传学
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免疫学
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生物信息学
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分子生物学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）