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circNDUFA13 通过与 STAT3 相互作用刺激骨髓间充质干细胞的成脂分化。

circNDUFA13 stimulates adipogenesis of bone marrow-derived mesenchymal stem cells via interaction with STAT3.

机构信息

Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, 332005, Jiangxi, China.

Jiujiang Key Laboratory of Rare Disease ResearchSchool of Basic Medical Sciences, Jiujiang University, Jiujiang, 332005, China.

出版信息

Sci Rep. 2024 Aug 26;14(1):19787. doi: 10.1038/s41598-024-70867-9.

DOI:10.1038/s41598-024-70867-9
PMID:39187566
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11347618/
Abstract

Circular RNAs (circRNAs) in controlling gene expression have been highlighted by increasing evidence, and their dysregulation has been linked to various diseases. However, the limited role of circRNAs in the adipogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) has been explored. High-throughput sequencing of circRNA was carried out on BMSCs and AD induction 7d BMSCs. Then a substantial upregulation of circNDUFA13 was detected among circRNAs in AD induction 7d BMSCs. We found that the adipogenic differentiation of BMSCs was positively linked with circNDUFA13 expression levels. Adipogenesis in BMSCs was effectively inhibited by circNDUFA13 knockdown, whereas overexpression of circNDUFA13 promoted adipogenesis. It was noted that circNDUFA13 regulated the adipogenic differentiation of BMSCs by directly interacting with the signal transducer and activator of transcription 3 (STAT3), which activates CEBPβ transcription. The in vitro model also validated the in vivo findings. our results suggest that circNDUFA13 controlled the adipogenic differentiation of BMSCs by targeting STAT3 and CEBPβ activation.

摘要

环状 RNA(circRNAs)在基因表达调控中的作用已被大量证据所强调,其失调与多种疾病有关。然而,circRNAs 在骨髓间充质干细胞(BMSCs)成脂分化中的作用有限。对 BMSCs 和 AD 诱导 7d BMSCs 进行了 circRNA 的高通量测序。然后在 AD 诱导 7d BMSCs 中的 circRNAs 中检测到 circNDUFA13 的大量上调。我们发现 BMSCs 的成脂分化与 circNDUFA13 表达水平呈正相关。circNDUFA13 的敲低有效抑制了 BMSCs 的成脂分化,而 circNDUFA13 的过表达则促进了成脂分化。值得注意的是,circNDUFA13 通过直接与信号转导和转录激活因子 3(STAT3)相互作用来调节 BMSCs 的成脂分化,从而激活 CEBPβ 转录。体外模型也验证了体内研究结果。我们的结果表明,circNDUFA13 通过靶向 STAT3 和 CEBPβ 的激活来控制 BMSCs 的成脂分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/f809a013a79b/41598_2024_70867_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/0d8705062c7b/41598_2024_70867_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/2e2735709646/41598_2024_70867_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/691db9763103/41598_2024_70867_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/7f7755055826/41598_2024_70867_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/f809a013a79b/41598_2024_70867_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/0d8705062c7b/41598_2024_70867_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/2e2735709646/41598_2024_70867_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/691db9763103/41598_2024_70867_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/7f7755055826/41598_2024_70867_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f77/11347618/f809a013a79b/41598_2024_70867_Fig5_HTML.jpg

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本文引用的文献

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Circular RNAs: biology and clinical significance of breast cancer.环状 RNAs:乳腺癌的生物学和临床意义。
RNA Biol. 2023 Jan;20(1):859-874. doi: 10.1080/15476286.2023.2272468. Epub 2023 Oct 26.
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Non-Coding RNAs and Adipogenesis.非编码 RNA 与脂肪生成。
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A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.环状 RNA 分子 circINSIG1 编码的一种新型蛋白可通过促进结直肠癌细胞中 INSIG1 的泛素依赖性降解来重新编程胆固醇代谢。
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circCAPRIN1 interacts with STAT2 to promote tumor progression and lipid synthesis via upregulating ACC1 expression in colorectal cancer.circCAPRIN1 通过上调结直肠癌中 ACC1 的表达与 STAT2 相互作用促进肿瘤进展和脂质合成。
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