Emerging roles of circRNAs in mice kidney with aging,Microscopy Research and Technique

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Emerging roles of circRNAs in mice kidney with aging
Microscopy Research and Technique ( IF 2.0 ) Pub Date : 2022-06-03 , DOI: 10.1002/jemt.24147
Fanfan Gao ₁ , Jie Li ₂ , Shanshan Liang ₃ , Limin Wei ₂ , Xin He ₂ , Sixiu Liu ₂ , Xin Cheng ₂ , Kehui Shi ₂ , Hongli Jiang ₂ , Lei Chen ₂

Affiliation

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.

中文翻译：

circRNA 在衰老小鼠肾脏中的新作用

环状RNA（circRNA）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，人们对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 测序从 3 个月、12 个月和 24 个月大的小鼠的肾脏中鉴定出 11,929 个 circRNA，其中 12 个 circRNA 通过 qPCR 验证。基于已验证的 circRNA 及其预测的 miRNA-mRNA 靶标对，进行了 circRNA-miRNA-mRNA 相互作用网络。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 circNpas2 作为中枢基因，该基因在衰老过程中在小鼠肾脏中显着降低。随后，我们发现细胞周期在 G1 期停滞，并且在 circNpas2 敲低的细胞中 P53 和 P16 的表达显着增加。此外，circNpas2 的敲低抑制了 ER 相关蛋白 HSPA5 和 ERO1L 的表达。总之，我们的研究结果有助于更好地了解 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。

更新日期：2022-06-03

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