TY - JOUR
T1 - Emerging roles of circRNAs in mice kidney with aging
AU - Gao, Fanfan
AU - Li, Jie
AU - Liang, Shanshan
AU - Wei, Limin
AU - He, Xin
AU - Liu, Sixiu
AU - Cheng, Xin
AU - Shi, Kehui
AU - Jiang, Hongli
AU - Chen, Lei
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/8
Y1 - 2022/8
N2 - Circular RNA (circRNA) is a novel type of noncoding RNA expressed in different tissues and species. Up to now, little is known of the function and expression of circRNAs in kidney aging. In this research, we used RNA sequencing to identify 11,929 circRNAs in kidney from 3-, 12-, and 24-month-old mice, of which 12 circRNAs were validated by qPCR. Based on the validated circRNAs and their predicted miRNA-mRNA target pairs, a circRNA-miRNA-mRNA interactions network was conducted. Bioinformatics analysis for all the mRNAs in the ceRNA network showed that the most enriched gene ontology (GO) term and one of the most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were associated with endoplasmic reticulum (ER). The network also identified circNpas2, which was decreased significantly in mice kidney during aging, as a hub gene. Subsequently, we found that the cell cycle was arrested in G1 phase and the expression of P53 and P16 increased significantly in the circNpas2-knockdown cells. Moreover, knockdown of circNpas2 inhibited expression of ER-related proteins, HSPA5 and ERO1L. Taken together, our findings contribute to a better understanding of the role played by circRNA during kidney aging and provide potential therapeutic targets for the prevention of kidney aging. Research Highlights: This study is the first to systematically analyze the dysregulated circRNAs and ceRNA network during renal aging. The dysregulated circRNAs during renal aging are most enriched in ER stress-related pathway. CircNpas2 regulates senescence in TCMK-1.
AB - Circular RNA (circRNA) is a novel type of noncoding RNA expressed in different tissues and species. Up to now, little is known of the function and expression of circRNAs in kidney aging. In this research, we used RNA sequencing to identify 11,929 circRNAs in kidney from 3-, 12-, and 24-month-old mice, of which 12 circRNAs were validated by qPCR. Based on the validated circRNAs and their predicted miRNA-mRNA target pairs, a circRNA-miRNA-mRNA interactions network was conducted. Bioinformatics analysis for all the mRNAs in the ceRNA network showed that the most enriched gene ontology (GO) term and one of the most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were associated with endoplasmic reticulum (ER). The network also identified circNpas2, which was decreased significantly in mice kidney during aging, as a hub gene. Subsequently, we found that the cell cycle was arrested in G1 phase and the expression of P53 and P16 increased significantly in the circNpas2-knockdown cells. Moreover, knockdown of circNpas2 inhibited expression of ER-related proteins, HSPA5 and ERO1L. Taken together, our findings contribute to a better understanding of the role played by circRNA during kidney aging and provide potential therapeutic targets for the prevention of kidney aging. Research Highlights: This study is the first to systematically analyze the dysregulated circRNAs and ceRNA network during renal aging. The dysregulated circRNAs during renal aging are most enriched in ER stress-related pathway. CircNpas2 regulates senescence in TCMK-1.
KW - circNpas2
KW - circular RNA
KW - competing endogenous RNA
KW - endoplasmic reticulum
KW - kidney aging
UR - https://www.scopus.com/pages/publications/85131172062
U2 - 10.1002/jemt.24147
DO - 10.1002/jemt.24147
M3 - 文章
C2 - 35656876
AN - SCOPUS:85131172062
SN - 1059-910X
VL - 85
SP - 2984
EP - 2996
JO - Microscopy Research and Technique
JF - Microscopy Research and Technique
IS - 8
ER -