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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 intracellular validation of candidate circRNAs in C1 and C4. Validation of intracellular circRNA was performed using quantitative polymerase chain reaction (qPCR; in triplicate) in three randomly selected RNA samples. The level of intracellular expression of the validated circRNA was the average of these three samples. Prior to determination of the average, the normalized intracellular expression was calculated by the ratio of intracellular expression to microarray expression. Four up-regulated circRNAs (circRNA100550, circRNA100783, circRNA101328 and circRNA102592) and two down-regulated circRNAs with Top-2 Degree (circRNA103741 and circRNA101318) were validated in C1, respectively (a). Simultaneously, the same four up-regulated circRNAs and another two down-regulated circRNAs with Top-2 degree (circRNA104096 and circRNA100264) were validated in C4, respectively (b). Shown from the figure, only circRNA100783 is significantly differentially-expressed in both C1 and C4. Therefore, we supposed circRNA 1000783 might be a potential biomarker of immunosenescence
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Fig1: The intracellular validation of candidate circRNAs in C1 and C4. Validation of intracellular circRNA was performed using quantitative polymerase chain reaction (qPCR; in triplicate) in three randomly selected RNA samples. The level of intracellular expression of the validated circRNA was the average of these three samples. Prior to determination of the average, the normalized intracellular expression was calculated by the ratio of intracellular expression to microarray expression. Four up-regulated circRNAs (circRNA100550, circRNA100783, circRNA101328 and circRNA102592) and two down-regulated circRNAs with Top-2 Degree (circRNA103741 and circRNA101318) were validated in C1, respectively (a). Simultaneously, the same four up-regulated circRNAs and another two down-regulated circRNAs with Top-2 degree (circRNA104096 and circRNA100264) were validated in C4, respectively (b). Shown from the figure, only circRNA100783 is significantly differentially-expressed in both C1 and C4. Therefore, we supposed circRNA 1000783 might be a potential biomarker of immunosenescence

Mentions: The relative intracellular expression (ratio of intracellular expression to microarray expression) of the aforementioned 8 circRNAs is shown in Fig. 1. At the intracellular level, we found that only circRNA100783 expression significantly differed between the C1and C4 groups. This indicated that the expression of circRNA100783 was affected by time (C4) and antigen exposure (C1) during CD28-related CD8(+)T cell ageing. Therefore, we propose that this circRNA100783 is a potential biomarker in ageing T lymphocytes.Fig. 1


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 intracellular validation of candidate circRNAs in C1 and C4. Validation of intracellular circRNA was performed using quantitative polymerase chain reaction (qPCR; in triplicate) in three randomly selected RNA samples. The level of intracellular expression of the validated circRNA was the average of these three samples. Prior to determination of the average, the normalized intracellular expression was calculated by the ratio of intracellular expression to microarray expression. Four up-regulated circRNAs (circRNA100550, circRNA100783, circRNA101328 and circRNA102592) and two down-regulated circRNAs with Top-2 Degree (circRNA103741 and circRNA101318) were validated in C1, respectively (a). Simultaneously, the same four up-regulated circRNAs and another two down-regulated circRNAs with Top-2 degree (circRNA104096 and circRNA100264) were validated in C4, respectively (b). Shown from the figure, only circRNA100783 is significantly differentially-expressed in both C1 and C4. Therefore, we supposed circRNA 1000783 might be a potential biomarker of immunosenescence
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: The intracellular validation of candidate circRNAs in C1 and C4. Validation of intracellular circRNA was performed using quantitative polymerase chain reaction (qPCR; in triplicate) in three randomly selected RNA samples. The level of intracellular expression of the validated circRNA was the average of these three samples. Prior to determination of the average, the normalized intracellular expression was calculated by the ratio of intracellular expression to microarray expression. Four up-regulated circRNAs (circRNA100550, circRNA100783, circRNA101328 and circRNA102592) and two down-regulated circRNAs with Top-2 Degree (circRNA103741 and circRNA101318) were validated in C1, respectively (a). Simultaneously, the same four up-regulated circRNAs and another two down-regulated circRNAs with Top-2 degree (circRNA104096 and circRNA100264) were validated in C4, respectively (b). Shown from the figure, only circRNA100783 is significantly differentially-expressed in both C1 and C4. Therefore, we supposed circRNA 1000783 might be a potential biomarker of immunosenescence
Mentions: The relative intracellular expression (ratio of intracellular expression to microarray expression) of the aforementioned 8 circRNAs is shown in Fig. 1. At the intracellular level, we found that only circRNA100783 expression significantly differed between the C1and C4 groups. This indicated that the expression of circRNA100783 was affected by time (C4) and antigen exposure (C1) during CD28-related CD8(+)T cell ageing. Therefore, we propose that this circRNA100783 is a potential biomarker in ageing T lymphocytes.Fig. 1

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