Emerging roles of circRNAs in mice kidney with aging
Emerging roles of circRNAs in mice kidney with aging
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circRNA 在小鼠肾脏衰老过程中的新作用
DOI：
10.1002/jemt.24147
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发表时间：
2022-06
影响因子：
2.5
通讯作者：
Lei Chen
中科院分区：
文献类型：
--
作者：
Fanfan Gao;Jie Li;Shanshan Liang;Limin Wei;Xin He;Sixiu Liu;Xin Cheng;Kehui Shi;Hongli Jiang;Lei Chen
环状RNA（circular RNA）是一种在不同组织和物种中表达的新型非编码RNA。到目前为止，对circRNA在肾脏衰老中的功能和表达知之甚少。在这项研究中，我们使用RNA测序来鉴定3个月、12个月和24个月大的小鼠肾脏中的11，929个circRNA，其中12个circRNA通过qPCR进行了验证。基于验证的circRNA及其预测的miRNA-mRNA靶对，进行了circRNA-miRNA-mRNA相互作用网络。对ceRNA网络中所有mRNA的生物信息学分析表明，最丰富的基因本体（GO）术语和最丰富的京都基因和基因组百科全书（KEGG）途径之一与内质网（ER）相关。该网络还确定了circNpas 2，它在衰老过程中在小鼠肾脏中显着减少，作为一个枢纽基因。随后，我们发现在circNpas 2-敲低的细胞中，细胞周期被阻滞在G1期，P53和P16的表达显著增加。此外，敲低circNpas 2抑制ER相关蛋白HSPA 5和ERO 1 L的表达。总之，我们的研究结果有助于更好地理解circRNA在肾脏衰老过程中所起的作用，并为预防肾脏衰老提供潜在的治疗靶点。
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.
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