Dataset Information

Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.

ABSTRACT:

Background

A largely unexplored area of research is the identification and characterization of circular RNA (circRNA) in cystic fibrosis (CF). This study is the first to identify and characterize alterations in circRNA expression in cells lacking CFTR function. The circRNA expression profiles in whole blood transcriptomes from CF patients homozygous for the pathogenetic variant F508delCFTR are compared to healthy controls.

Methods

We developed a circRNA pipeline called circRNAFlow utilizing Nextflow. Whole blood transcriptomes from CF patients homozygous for the F508delCFTR-variant and healthy controls were utilized as input to circRNAFlow to discover dysregulated circRNA expression in CF samples compared to wild-type controls. Pathway enrichment analyzes were performed to investigate potential functions of dysregulated circRNAs in whole blood transcriptomes from CF samples compared to wild-type controls.

Results

A total of 118 dysregulated circRNAs were discovered in whole blood transcriptomes from CF patients homozygous for the F508delCFTR variant compared to healthy controls. 33 circRNAs were up regulated whilst 85 circRNAs were down regulated in CF samples compared to healthy controls. The overrepresented pathways of the host genes harboring dysregulated circRNA in CF samples compared to controls include positive regulation of responses to endoplasmic reticulum stress, intracellular transport, protein serine/threonine kinase activity, phospholipid-translocating ATPase complex, ferroptosis and cellular senescence. These enriched pathways corroborate the role of dysregulated cellular senescence in CF.

Conclusion

This study highlights the underexplored roles of circRNAs in CF with a perspective to provide a more complete molecular characterization of CF.

SUBMITTER: Salinas EA

PROVIDER: S-EPMC10947771 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.

Salinas Edward A EA Macauley Victor V Keeling Kim M KM Edwards Yvonne J K YJK

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20230502 4

<h4>Background</h4>A largely unexplored area of research is the identification and characterization of circular RNA (circRNA) in cystic fibrosis (CF). This study is the first to identify and characterize alterations in circRNA expression in cells lacking CFTR function. The circRNA expression profiles in whole blood transcriptomes from CF patients homozygous for the pathogenetic variant F508delCFTR are compared to healthy controls.<h4>Methods</h4>We developed a circRNA pipeline called circRNAFlow ...[more]

PMID: 37142522

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Project description:BackgroundPost-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear.MethodsTo understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF).ResultsHypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[-] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[-] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[-]. Compared to hypoglycemia[-] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC0-30min). ISR-AUC120-180min was not different in hypoglycemia[+] vs hypoglycemia[-] with abnormal glucose tolerance (AGT); however, glucose-AUC120-180min was lower in hypoglycemia[+] vs hypoglycemia[-] AGT. After adjusting for glucose-AUC, hypoglycemia[+] subjects tended to have higher ISR-AUC120-180min than hypoglycemia[-] AGT. Glucagon concentration did not differ between groups. Lower GLP-1-AUC30min and AUC180min and higher GIP-AUC30min were present in hypoglycemia[+] individuals.ConclusionHypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC30min), and possibly late compensatory hyperinsulinemia. Further study is required to understand whether absence of glucagon difference in the hypoglycemia[+] individuals signals counterregulatory impairment, to delineate the role of incretins in hypoglycemia, and to determine the relationship of hypoglycemia to emergence of CFRD.

Project description:BackgroundDifferently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC.MethodsWe investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs.ResultsIn total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78-0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75-0.96]) for hsa_circRNA_007148.DiscussionThe study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.

Dataset Information

Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.

Background

Methods

Results

Conclusion

Publications

Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.

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