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Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing.

Wang YH, Yu XH, Luo SS, Han H - Immun Ageing (2015)

Bottom Line: Of these, only circular RNA100783 exhibited significant validation.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.The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, First Affiliated Hospital of Harbin Medical University, Harbin, 15001 China ; First Institute of Geriatrics and Gerontology of Harbin Medical University, Harbin, 15001 China.

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.

No MeSH data available.


Related in: MedlinePlus

The biomathematical predicted circ000783-targeted circRNA-miRNA-mRNA/gene network. The circ000783-targeted circRNA-miRNA-mRNA/gene network is predicted based on sequence-pairing prediction. There are 73 miRNAs and 1930 genes being targeted in the present circ000783--miRNA-mRNA/gene network (miRNA-dependent cutoff value -0.11, mRNA-dependent cutoff value -0.38). Shown in this figure, miR-125a-5p exhibited the highest degree, followed by miR-33a-5p,miR-33b-5p,miR-580-3p,miR-499a-5p and miR-34b-3p
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Fig2: The biomathematical predicted circ000783-targeted circRNA-miRNA-mRNA/gene network. The circ000783-targeted circRNA-miRNA-mRNA/gene network is predicted based on sequence-pairing prediction. There are 73 miRNAs and 1930 genes being targeted in the present circ000783--miRNA-mRNA/gene network (miRNA-dependent cutoff value -0.11, mRNA-dependent cutoff value -0.38). Shown in this figure, miR-125a-5p exhibited the highest degree, followed by miR-33a-5p,miR-33b-5p,miR-580-3p,miR-499a-5p and miR-34b-3p

Mentions: According to the initial array data analysis, the genomic locus of circRNA100783 is on chromosome 11and the predicted sequence of the best linear transcript isuc001mul.1. The molecular interaction of circRNA100783 with its Top-5 miRNA targets is depicted in Additional file 1: Table S4. Supposing that circRNA100783 is an upstream molecular sponge in its circRNA-miRNA-mRNA network, we predicted a circRNA100783-miRNA-gene network using Targetscan and miRanda. A total of Top-18 miRNAs (miRNA-dependent cutoff value -0.11) andTop-6 miRNAs (mRNA-dependent cutoff value -0.38) were finally determined in this network (Fig. 2). Using DAVID function annotation, circRNA100783 was predicted to be associated most strongly with alternative splicing, as well as with splice variation and phosphoprotein function (Additional file 3: Figure S7). Given the strong correlation of the biogenesis of circRNAs with splicing and splice variation, it is possible that circRNA100783 functions in the regulation of a phosphoprotein that is involved in a molecular mechanism that leads to the age-related phenotypic loss of CD28 from CD8(+) T cells.Fig. 2


Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing.

Wang YH, Yu XH, Luo SS, Han H - Immun Ageing (2015)

The biomathematical predicted circ000783-targeted circRNA-miRNA-mRNA/gene network. The circ000783-targeted circRNA-miRNA-mRNA/gene network is predicted based on sequence-pairing prediction. There are 73 miRNAs and 1930 genes being targeted in the present circ000783--miRNA-mRNA/gene network (miRNA-dependent cutoff value -0.11, mRNA-dependent cutoff value -0.38). Shown in this figure, miR-125a-5p exhibited the highest degree, followed by miR-33a-5p,miR-33b-5p,miR-580-3p,miR-499a-5p and miR-34b-3p
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597608&req=5

Fig2: The biomathematical predicted circ000783-targeted circRNA-miRNA-mRNA/gene network. The circ000783-targeted circRNA-miRNA-mRNA/gene network is predicted based on sequence-pairing prediction. There are 73 miRNAs and 1930 genes being targeted in the present circ000783--miRNA-mRNA/gene network (miRNA-dependent cutoff value -0.11, mRNA-dependent cutoff value -0.38). Shown in this figure, miR-125a-5p exhibited the highest degree, followed by miR-33a-5p,miR-33b-5p,miR-580-3p,miR-499a-5p and miR-34b-3p
Mentions: According to the initial array data analysis, the genomic locus of circRNA100783 is on chromosome 11and the predicted sequence of the best linear transcript isuc001mul.1. The molecular interaction of circRNA100783 with its Top-5 miRNA targets is depicted in Additional file 1: Table S4. Supposing that circRNA100783 is an upstream molecular sponge in its circRNA-miRNA-mRNA network, we predicted a circRNA100783-miRNA-gene network using Targetscan and miRanda. A total of Top-18 miRNAs (miRNA-dependent cutoff value -0.11) andTop-6 miRNAs (mRNA-dependent cutoff value -0.38) were finally determined in this network (Fig. 2). Using DAVID function annotation, circRNA100783 was predicted to be associated most strongly with alternative splicing, as well as with splice variation and phosphoprotein function (Additional file 3: Figure S7). Given the strong correlation of the biogenesis of circRNAs with splicing and splice variation, it is possible that circRNA100783 functions in the regulation of a phosphoprotein that is involved in a molecular mechanism that leads to the age-related phenotypic loss of CD28 from CD8(+) T cells.Fig. 2

Bottom Line: Of these, only circular RNA100783 exhibited significant validation.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.The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, First Affiliated Hospital of Harbin Medical University, Harbin, 15001 China ; First Institute of Geriatrics and Gerontology of Harbin Medical University, Harbin, 15001 China.

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.

No MeSH data available.


Related in: MedlinePlus