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Published on: December 21, 2016
Differential Profile of Plasma Circular RNAs in Type 1 Diabetes Mellitus
Yangyang Li1, Ying Zhou2, Minghui Zhao1
1Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China.
Background:
No currently available biomarkers or treatment regimens fully meet therapeutic needs of type 1 diabetes mellitus (T1DM). Circular RNA (circRNA) is a recently identified class of stable noncoding RNA that have been documented as potential biomarkers for various diseases. Our objective was to identify and analyze plasma circRNAs altered in T1DM.
Methods:
We used microarray to screen differentially expressed plasma circRNAs in patients with new onset T1DM (n=3) and age-/gender-matched healthy controls (n=3). Then, we selected six candidates with highest fold-change and validated them by quantitative real-time polymerase chain reaction in independent human cohort samples (n=12). Bioinformatic tools were adopted to predict putative microRNAs (miRNAs) sponged by these validated circRNAs and their downstream messenger RNAs (mRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to gain further insights into T1DM pathogenesis.
Results:
We identified 68 differentially expressed circRNAs, with 61 and seven being up- and downregulated respectively. Four of the six selected candidates were successfully validated. Curations of their predicted interacting miRNAs revealed critical roles in inflammation and pathogenesis of autoimmune disorders. Functional relations were visualized by a circRNA-miRNA-mRNA network. GO and KEGG analyses identified multiple inflammation-related processes that could be potentially associated with T1DM pathogenesis, including cytokine-cytokine receptor interaction, inflammatory mediator regulation of transient receptor potential channels and leukocyte activation involved in immune response.
Conclusion:
Our study report, for the first time, a profile of differentially expressed plasma circRNAs in new onset T1DM. Further in silico annotations and bioinformatics analyses supported future application of circRNAs as novel biomarkers of T1DM.
Insights
Circular RNAs (circRNAs) show altered expression in new-onset type 1 diabetes mellitus (T1DM). These findings suggest circRNAs could serve as novel biomarkers for T1DM diagnosis and understanding disease mechanisms.
Area of Science:
- Genomics
- Molecular Biology
- Biochemistry
Background:
- Type 1 diabetes mellitus (T1DM) lacks sufficient biomarkers and effective treatments.
- Circular RNAs (circRNAs) are stable noncoding RNAs with potential as disease biomarkers.
- Investigating plasma circRNAs in T1DM is crucial for advancing diagnostics and therapeutics.
Purpose of the Study:
- To identify and analyze differentially expressed plasma circRNAs in new-onset T1DM.
- To explore the potential of circRNAs as biomarkers for T1DM.
- To elucidate the role of circRNAs in T1DM pathogenesis through bioinformatics analysis.
Main Methods:
- Microarray screening of plasma circRNAs in T1DM patients and healthy controls.
- Validation of candidate circRNAs using quantitative real-time polymerase chain reaction.
- Bioinformatic prediction of circRNA-miRNA-mRNA interactions and pathway analysis (GO, KEGG).
Main Results:
- Identified 68 differentially expressed circRNAs in new-onset T1DM.
- Validated four key circRNA candidates.
- Predicted interactions suggest roles in inflammation and autoimmune pathogenesis.
- Pathway analysis highlighted inflammation-related processes in T1DM.
Conclusions:
- This study presents the first profile of differentially expressed plasma circRNAs in new-onset T1DM.
- CircRNAs show promise as novel biomarkers for T1DM.
- Further research into circRNA function can illuminate T1DM pathogenesis.
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