Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell
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IMMUNITY & AGEING
RESEARCH
Open Access
Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing Yu-hong Wang1,2, Xu-hui Yu3, Shan-shun Luo1,2 and Hui Han1,2*
Abstract Background: Ageing brings about the gradual deterioration of the immune system, also known as immunosenescence. The role of non-coding circular RNA in immunosenescence is under studied. Using circular RNA microarray data, we assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+) T cells isolated from healthy elderly or adult control subjects. Using a step-wise biomathematical strategy, the differentially-expressed circRNAs were identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4 (CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed circRNA species from these profiles were optimized as immunosenescence biomarkers. Results: Four overlapping upregulated circular RNAs (100550, 100783, 101328 and 102592) expressed in cross-comparison between C1 and C4 were validated using quantitative polymerase chain reaction. Of these, only circular RNA100783 exhibited significant validation. None of the down-regulated circular RNAs were expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted circular RNA100783-targeted miRNA-gene interactions using online DAVID annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA network may be involved in alternative splicing, the production of splice variants, and in the regulation of phosphoprotein expression. Considering the hypothesis of splicing-related biogenesis of circRNAs, we propose that circular RNA100783 may play a role in phosphoprotein-associated functions duringCD28-related CD8(+) T cell ageing. Conclusions: This study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression. The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence. Keywords: T cell, Ageing, CD28, Circular RNA, Microarray, Biomathematics
Background The ongoing loss of immune function during ageing, or immunosenescence, is a major contributor to the increasing morbidity and mortality in the elderly population. One of the prominent alterations on immune cells during this * Correspondence: [email protected] Xu-hui Yu contributed as the co-first author. 1 Department of Geriatrics, First Affiliated Hospital of Harbin Medical University, Harbin 15001, China 2 First Institute of Geriatrics and Gerontology of Harbin Medical University, Harbin 15001, China Full list of author information is available at the end of the article
process is the gradual loss of the co-stimulatory molecule, CD28, from the surface of CD8(+) T lymphocytes [1, 2].
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