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tRNA 衍生片段的表达谱及其在人类静脉曲张中的潜在作用。

Expression profile of tRNA‑derived fragments and their potential roles in human varicose veins.

机构信息

Department of Vascular Surgery, Shanghai East Hospital Affiliated to Tongji University School of Medicine, Shanghai 200120, P.R. China.

Department of Cardiovascular Surgery, Shanghai East Hospital Affiliated to Tongji University School of Medicine, Shanghai 200120, P.R. China.

出版信息

Mol Med Rep. 2019 Oct;20(4):3191-3201. doi: 10.3892/mmr.2019.10544. Epub 2019 Aug 1.

Abstract

Varicose veins (VVs) is a common disease presenting with chronic venous insufficiency. tRNA‑derived fragments (tRFs) are associated with a variety of pathological conditions. However, the functions of tRFs in VVs have not been elucidated to date. The present study aimed to identify the key tRFs and investigate their potential roles in VVs. Small RNA sequencing (RNA‑seq) was performed to investigate the expression of tRFs in tissues of patients with VVs and their matched adjacent normal veins tissues (ANVs). Reverse transcription‑quantitative PCR (RT‑qPCR) was used to confirm the differential expression of tRFs. A total of 13,789 tRFs were identified by small RNA‑seq, including 45 differentially expressed tRFs (DETs), which comprised 14 upregulated and 31 downregulated tRFs in VV tissues compared with ANVs. In addition, DETs were mainly involved in the function of epidermal growth factor receptor and vascular endothelial growth factor receptor signaling pathways in VVs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes of DETs were predominantly involved in Wnt and mitogen‑activated protein kinase (MAPK) signaling pathways, as well as calcium signaling. Additionally, two upregulated tRFs (tRF‑36‑F900BY4D84KRIME and tRF‑23‑87R8WP9IY) and one downregulated tRF (tRF‑40‑86J8WPMN1E8Y7Z2R) were further validated by RT‑qPCR, and a signaling pathway regulation network of their target genes confirmed their involvement in the calcium, Wnt and MAPK signaling pathways. The results of the present study identified three DETs (tRF‑36‑F900BY4D84KRIME, tRF‑23‑87R8WP9IY and tRF‑40‑86J8WPMN1E8Y7Z2R), which may have crucial roles in the occurrence and progression of VVs by regulating Wnt and MAPK signaling, as well as calcium signaling. The present results may provide a basis for further investigation of the functional roles of tRFs in VVs.

摘要

静脉曲张(VV)是一种常见的慢性静脉功能不全疾病。转移 RNA 衍生片段(tRFs)与多种病理状况有关。然而,tRFs 在 VV 中的功能尚未得到阐明。本研究旨在鉴定关键 tRFs 并研究其在 VV 中的潜在作用。通过小 RNA 测序(RNA-seq)研究 VV 患者组织及其匹配的相邻正常静脉组织(ANV)中 tRFs 的表达。采用逆转录-定量 PCR(RT-qPCR)验证 tRFs 的差异表达。通过小 RNA-seq 鉴定出 13789 个 tRFs,包括 45 个差异表达的 tRFs(DETs),与 ANV 相比,VV 组织中 14 个上调和 31 个下调的 tRFs。此外,DETs 主要参与 VV 中表皮生长因子受体和血管内皮生长因子受体信号通路的功能。京都基因与基因组百科全书(KEGG)分析显示,DETs 的靶基因主要参与 Wnt 和丝裂原激活蛋白激酶(MAPK)信号通路以及钙信号。此外,通过 RT-qPCR 进一步验证了两个上调的 tRF(tRF-36-F900BY4D84KRIME 和 tRF-23-87R8WP9IY)和一个下调的 tRF(tRF-40-86J8WPMN1E8Y7Z2R),并通过其靶基因的信号通路调控网络证实它们参与钙、Wnt 和 MAPK 信号通路。本研究鉴定出三个 DETs(tRF-36-F900BY4D84KRIME、tRF-23-87R8WP9IY 和 tRF-40-86J8WPMN1E8Y7Z2R),它们可能通过调节 Wnt 和 MAPK 信号以及钙信号在 VV 的发生和发展中发挥关键作用。本研究结果可能为进一步研究 tRFs 在 VV 中的功能作用提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bca1/6755252/8fbd6e7a7da3/MMR-20-04-3191-g00.jpg

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