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环状 RNA hsa_circ_105039 通过海绵吸附 miR-17 调控细胞周期蛋白 D2 的表达促进心肌细胞分化。

Circular RNA hsa_circ_105039 promotes cardiomyocyte differentiation by sponging miR‑17 to regulate cyclinD2 expression.

机构信息

Department of Pediatrics, Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China.

出版信息

Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12501. Epub 2021 Oct 19.

DOI:10.3892/mmr.2021.12501
PMID:34664684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8548937/
Abstract

Previously it was found that hsa_circ_105039 was underexpressed in the heart tissue of patients with congenital heart disease (CHD). However, the function and mechanism of hsa_circ_105039 in CHD are unclear. In the present study, induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes using 1% dimethyl sulfoxide (DMSO). Cell differentiation, viability, migration and apoptosis were measured before and following hsa_circ_105039 knockdown or overexpression. The results indicated that hsa_circ_105039 overexpression promoted cell differentiation, viability and migration; whereas apoptosis was simultaneously repressed. A luciferase reporter assay verified that hsa_circ_105039 acted as a sponge for microRNA (miR)‑17 and that cyclinD2 was a direct target of miR‑17. Furthermore, differentiation‑related genes and proteins were analyzed by reverse transcription‑quantitative PCR and western blotting, respectively. The results showed that hsa_circ_105039 could also upregulate the expression of differentiation‑related genes and proteins, including natriuretic peptide A, cardiac troponin I, GATA‑binding protein 4 and homobox transcription factor, in iPS cells. The results suggested that hsa_circ_105039 exerted a protective effect by promoting miR‑17/cyclinD2 in DMSO‑induced iPS cardiomyocytes, which indicated that hsa_circ_105039 is a potential key molecule for the diagnosis of CHD.

摘要

先前发现 hsa_circ_105039 在先天性心脏病 (CHD) 患者的心脏组织中表达下调。然而，hsa_circ_105039 在 CHD 中的功能和机制尚不清楚。在本研究中，使用 1%二甲基亚砜 (DMSO) 将诱导多能干细胞 (iPS) 分化为心肌细胞。在 hsa_circ_105039 敲低或过表达前后测量细胞分化、活力、迁移和凋亡。结果表明，hsa_circ_105039 过表达促进细胞分化、活力和迁移，同时抑制凋亡。荧光素酶报告基因检测证实 hsa_circ_105039 作为 microRNA (miR)‑17 的海绵，cyclinD2 是 miR‑17 的直接靶标。此外，通过逆转录-定量 PCR 和 Western blot 分别分析分化相关基因和蛋白。结果表明，hsa_circ_105039 还可以上调 iPS 细胞中分化相关基因和蛋白的表达，包括脑钠肽 A、心肌肌钙蛋白 I、GATA 结合蛋白 4 和同源盒转录因子。结果表明，hsa_circ_105039 通过促进 DMSO 诱导的 iPS 心肌细胞中的 miR-17/cyclinD2 发挥保护作用，表明 hsa_circ_105039 是 CHD 诊断的潜在关键分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/8ddcdeae4500/mmr-24-06-12501-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/95acda22d6ce/mmr-24-06-12501-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/830af4f10f15/mmr-24-06-12501-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/ca5b8b23924a/mmr-24-06-12501-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/0f5626596be2/mmr-24-06-12501-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/8ddcdeae4500/mmr-24-06-12501-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/95acda22d6ce/mmr-24-06-12501-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/830af4f10f15/mmr-24-06-12501-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/ca5b8b23924a/mmr-24-06-12501-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/0f5626596be2/mmr-24-06-12501-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1192/8548937/8ddcdeae4500/mmr-24-06-12501-g04.jpg

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