Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease

Heydari, Raheleh; Karimi, Padideh; Meyfour, Anna

doi:10.1016/j.biopha.2024.116868

Biomedicine & Pharmacotherapy

2024

DOI: 10.1016/j.biopha.2024.116868

|View full text |Cite

Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease

Raheleh Heydari,

Padideh Karimi,

Anna Meyfour

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

References 201 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Targeting TSPEAR-AS2 suppresses tumor growth and interferon signaling in esophageal cancer

Zhang,

Cui

2024

Sci Rep

View full text Add to dashboard Cite

Dysregulation of long non-coding RNAs (lncRNAs) and interferon signaling contributes to tumorigenesis and progression; however, their crosstalk in tumor biology remains poorly understood. Here, we showed that TSPEAR-AS2, an lncRNA mediated by METTL1, activates the interferon signaling pathway in esophageal cancer (ESCA). Clinically, we conducted a pan-cancer investigation and identified TSPEAR-AS2 as a novel ESCA-related lncRNA that predicts a worse patient prognosis. The high expression of TSPEAR-AS2 was validated in multiple ESCA cohorts, demonstrating that this lncRNA had good diagnostic performance. METTL1, an RNA N7-methylguanosine (m7G) methyltransferase, was positively correlated with TSPEAR-AS2 expression in ESCA tissues, and METTL1 was found to induce TSPEAR-AS2 expression in ESCA cells. Functionally, the up-regulation of TSPEAR-AS2 promoted proliferation, cell cycle progression, migration, and stemness in ESCA cells, whereas its knockdown attenuated these malignant phenotypes. Furthermore, both TSPEAR-AS2 deficiency and antisense oligonucleotide (ASO)-based intratumoral intervention could significantly suppress tumor growth in vivo. Mechanistically, quantitative proteomic analysis revealed that TSPEAR-AS2 ablation altered the expression of functional proteins related to interferon signaling pathways, such as HLA-E, IRF3, and IFITs. These findings identify a previously unrecognized role of the METTL1/TSPEAR-AS2/interferon signaling axis in ESCA development and suggest that TSPEAR-AS2 is a potential prognostic indicator and therapeutic vulnerability for this malignancy.

show abstract

Targeting TSPEAR-AS2 suppresses tumor growth and interferon signaling in esophageal cancer

Zhang,

Cui

2024

Sci Rep

View full text Add to dashboard Cite

show abstract

Nonlesional ileal transcriptome in Crohn's disease reveals alterations in immune response and metabolic pathway

Lee,

Baek

et al. 2024

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and AimWe aimed to assess the gene expression profiles of nonlesional small bowels in patients with Crohn's disease (CD) to identify its accompanying molecular alterations.MethodsWe performed RNA sequencing of the uninflamed small bowel tissues obtained from 70 patients with ileal CD and 9 patients with colon cancer (non‐CD controls) during bowel resection. Differentially expressed gene (DEG) analyses were performed using DESeq2. Gene set enrichment, correlation, and cell deconvolution analyses were applied to identify modules and functionally enriched transcriptional signatures of CD.ResultsA comparison of CD patients and non‐CD controls revealed that of the 372 DEGs, 49 protein‐coding genes and 5 long non‐coding RNAs overlapped with the inflammatory bowel disease susceptibility loci. The pathways related to immune and inflammatory reactions were upregulated in CD, while metabolic pathways were downregulated in CD. Compared with non‐CD controls, CD patients had significantly higher proportions of immune cells, including plasma cells (P = 1.15 × 10−4), and a lower proportion of epithelial cells (P = 1.12 × 10−4). Co‐upregulated genes (M14 module) and co‐downregulated genes (M9 module) were identified in CD patients. The M14 module was enriched in immune‐related genes and significantly associated with the responses to anti‐tumor necrosis factor (TNF) therapy. The core signature of the M14 module was comprised of six genes and was upregulated in nonresponders to anti‐TNF therapy of five independent cohorts (n = 163), indicating acceptable discrimination ability (area under the receiver operating characteristic curve of 75–86%).ConclusionsThe differences in gene expression and cellular composition between CD patients and non‐CD controls imply significant molecular alterations, which are associated with the response to anti‐TNF treatment.

show abstract

Identifying the ceRNA Regulatory Network in Early-Stage Acute Pancreatitis and Investigating the Therapeutic Potential of NEAT1 in Mouse Models

Lin,

Huang

2024

JIR

View full text Add to dashboard Cite

Purpose Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP). Methods In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP). Results Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models. Conclusion We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease

Cited by 3 publications

References 201 publications

Targeting TSPEAR-AS2 suppresses tumor growth and interferon signaling in esophageal cancer

Targeting TSPEAR-AS2 suppresses tumor growth and interferon signaling in esophageal cancer

Nonlesional ileal transcriptome in Crohn's disease reveals alterations in immune response and metabolic pathway

Identifying the ceRNA Regulatory Network in Early-Stage Acute Pancreatitis and Investigating the Therapeutic Potential of NEAT1 in Mouse Models

Contact Info

Product

Resources

About