• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

肌生成相关 miRNA 对 JNK/MAPK 信号通路的抑制作用是骨骼肌发育所必需的。

Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development.

机构信息

Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.

Vaccine Research Institute of Sun Yat-Sen University, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.

出版信息

Cell Death Differ. 2018 Sep;25(9):1581-1597. doi: 10.1038/s41418-018-0063-1. Epub 2018 Feb 15.

DOI:10.1038/s41418-018-0063-1
PMID:29449644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6143622/
Abstract

Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted. Our study revealed a novel double-negative feedback regulatory pattern of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade responsible for skeletal muscle development.

摘要

骨骼肌分化受多种细胞信号通路控制，但 JNK/MAPK 信号通路在这一过程中的主导作用尚未完全阐明。在这里，我们报告 JNK/MAPK 通路在成肌细胞晚期显著下调，与 P38/MAPK 通路相反，它负调控骨骼肌分化。基于 PAR-CLIP-seq 分析，我们鉴定出六个上调的 miRNA（miR-1a-3p、miR-133a-3p、miR-133b-3p、miR-206-3p、miR-128-3p、miR-351-5p），即成肌相关 miRNA（mamiRs），通过抑制 JNK/MAPK 通路磷酸化的多个因子，负调控 JNK/MAPK 通路，包括 MEKK1、MEKK2、MKK7 和 c-Jun，但不是 JNK 蛋白本身，从而进一步促进转录因子 MyoD 和 mamiRs 的表达。我们的研究揭示了一种新的细胞特异性 miRNA 通过靶向负责骨骼肌发育的磷酸化激酶信号级联的双重负反馈调控模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/d06be08f5bcf/41418_2018_63_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/d7e6a83f6b9b/41418_2018_63_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/6eec6e3fe173/41418_2018_63_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/2b2f4a965619/41418_2018_63_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/5ad115ae505c/41418_2018_63_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/88612c58a357/41418_2018_63_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/93559ff8d53f/41418_2018_63_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/25f10e76a612/41418_2018_63_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/d06be08f5bcf/41418_2018_63_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/d7e6a83f6b9b/41418_2018_63_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/6eec6e3fe173/41418_2018_63_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/2b2f4a965619/41418_2018_63_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/5ad115ae505c/41418_2018_63_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/88612c58a357/41418_2018_63_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/93559ff8d53f/41418_2018_63_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/25f10e76a612/41418_2018_63_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d06/6143622/d06be08f5bcf/41418_2018_63_Fig8_HTML.jpg

相似文献

1
Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development.肌生成相关 miRNA 对 JNK/MAPK 信号通路的抑制作用是骨骼肌发育所必需的。
Cell Death Differ. 2018 Sep;25(9):1581-1597. doi: 10.1038/s41418-018-0063-1. Epub 2018 Feb 15.
2
Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway.胍基乙酸通过 miR-133a-3p 和 miR-1a-3p 共同介导的 Akt/mTOR/S6K 信号通路调控成肌分化和肌肉生长。
Int J Mol Sci. 2018 Sep 19;19(9):2837. doi: 10.3390/ijms19092837.
3
MiR-501-3p Forms a Feedback Loop with FOS, MDFI, and MyoD to Regulate C2C12 Myogenesis.miR-501-3p 与 FOS、MDFI 和 MyoD 形成反馈环路调节 C2C12 成肌分化。
Cells. 2019 Jun 11;8(6):573. doi: 10.3390/cells8060573.
4
MEKK1 signaling through p38 leads to transcriptional inactivation of E47 and repression of skeletal myogenesis.通过p38的MEKK1信号传导导致E47的转录失活和骨骼肌生成的抑制。
J Biol Chem. 2004 Jul 23;279(30):30966-72. doi: 10.1074/jbc.M402224200. Epub 2004 May 24.
5
MicroRNA-181a Regulates Apoptosis and Autophagy Process in Parkinson's Disease by Inhibiting p38 Mitogen-Activated Protein Kinase (MAPK)/c-Jun N-Terminal Kinases (JNK) Signaling Pathways.微小RNA-181a通过抑制p38丝裂原活化蛋白激酶（MAPK）/c-Jun氨基末端激酶（JNK）信号通路调节帕金森病中的细胞凋亡和自噬过程。
Med Sci Monit. 2017 Apr 2;23:1597-1606. doi: 10.12659/msm.900218.
6
The functional analysis of transiently upregulated miR-101 suggests a "braking" regulatory mechanism during myogenesis.瞬时上调的miR-101的功能分析表明，在肌肉生成过程中存在一种“制动”调节机制。
Sci China Life Sci. 2021 Oct;64(10):1612-1623. doi: 10.1007/s11427-020-1856-5. Epub 2021 Jan 27.
7
A Phosphoproteomic Screen Identifies a Guanine Nucleotide Exchange Factor for Rab3A Protein as a Mitogen-activated Protein (MAP) Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis.磷酸化蛋白质组学筛选鉴定出一种Rab3A蛋白的鸟嘌呤核苷酸交换因子，作为丝裂原活化蛋白（MAP）激酶磷酸酶-5调节的MAP激酶靶点，参与白细胞介素6（IL-6）分泌和肌生成过程。
J Biol Chem. 2017 Mar 3;292(9):3581-3590. doi: 10.1074/jbc.M116.769208. Epub 2017 Jan 17.
8
MicroRNA-494-3p inhibits formation of fast oxidative muscle fibres by targeting E1A-binding protein p300 in human-induced pluripotent stem cells.miRNA-494-3p 通过靶向人诱导多能干细胞中的 E1A 结合蛋白 p300 抑制快氧化肌纤维的形成。
Sci Rep. 2021 Jan 13;11(1):1161. doi: 10.1038/s41598-020-80742-y.
9
Effects of insulin, contraction, and phorbol esters on mitogen-activated protein kinase signaling in skeletal muscle from lean and ob/ob mice.胰岛素、收缩及佛波酯对瘦型和ob/ob小鼠骨骼肌中丝裂原活化蛋白激酶信号传导的影响。
Diabetes. 2004 Jun;53(6):1436-44. doi: 10.2337/diabetes.53.6.1436.
10
Downregulation of microRNA-143-5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen-activated protein kinases 14-dependent p38 mitogen-activated protein kinases signaling pathway.下调 microRNA-143-5p 是通过激活丝裂原活化蛋白激酶 14 依赖的 p38 丝裂原活化蛋白激酶信号通路促进人牙髓干细胞成牙本质细胞分化所必需的。
J Cell Physiol. 2019 Apr;234(4):4840-4850. doi: 10.1002/jcp.27282. Epub 2018 Oct 26.

引用本文的文献

1
Stage-specific requirement for METTL3-dependent mA epitranscriptomic regulation during myogenesis.成肌过程中METTL3依赖的m⁶A表观转录组调控的阶段特异性需求。
Commun Biol. 2025 Aug 30;8(1):1317. doi: 10.1038/s42003-025-08759-5.
2
Melatonin-mediated Inhibition of XPO5 phosphorylation facilitates the chondrogenic differentiation of human bone marrow mesenchymal stem cells by regulating the transport of miR-590-5p.褪黑素介导的XPO5磷酸化抑制通过调节miR-590-5p的转运促进人骨髓间充质干细胞的软骨分化。
Mol Biol Rep. 2025 Jun 23;52(1):626. doi: 10.1007/s11033-025-10720-y.
3
Characterization and analysis of MicroRNA during leg muscle development in embryonic stage of daozhou grey goose.

本文引用的文献

1
Influence of Nitric Oxide generated through microwave plasma on L6 skeletal muscle cell myogenesis via oxidative signaling pathways.通过微波等离子体产生的一氧化氮对 L6 骨骼肌细胞成肌作用的影响及其氧化信号通路。
Sci Rep. 2017 Apr 3;7(1):542. doi: 10.1038/s41598-017-00154-3.
2
Immobilization rapidly induces muscle insulin resistance together with the activation of MAPKs (JNK and p38) and impairment of AS160 phosphorylation.制动迅速诱导肌肉胰岛素抵抗，同时激活丝裂原活化蛋白激酶（JNK和p38）并损害AS160磷酸化。
Physiol Rep. 2016 Aug;4(15). doi: 10.14814/phy2.12876.
3
Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting.
道州灰鹅胚胎期腿部肌肉发育过程中MicroRNA的鉴定与分析
Poult Sci. 2025 Jun 5;104(9):105354. doi: 10.1016/j.psj.2025.105354.
4
CircRNA profiling of skeletal muscle satellite cells in goats reveals circTGFβ2 promotes myoblast differentiation.环状 RNA 谱分析山羊骨骼肌卫星细胞显示环状 TGFβ2 促进成肌细胞分化。
BMC Genomics. 2024 Nov 12;25(1):1075. doi: 10.1186/s12864-024-11008-4.
5
A mutation with knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia.CRISPR/Cas9 基因编辑技术敲除绵羊突变体促进骨骼肌肌纤维增生。
Elife. 2024 Oct 4;12:RP86827. doi: 10.7554/eLife.86827.
6
Transcriptome sequencing reveals the potential mechanisms of dietary lutein regulation on chicken leg muscle development.转录组测序揭示了日粮叶黄素调控鸡腿肌肉发育的潜在机制。
Poult Sci. 2024 Dec;103(12):104265. doi: 10.1016/j.psj.2024.104265. Epub 2024 Aug 24.
7
Exploring the versatility of miRNA-128: a comprehensive review on its role as a biomarker and therapeutic target in clinical pathways.探索 miRNA-128 的多功能性：miRNA-128 作为生物标志物和治疗靶点在临床途径中的作用的综合综述。
Mol Biol Rep. 2024 Jul 28;51(1):860. doi: 10.1007/s11033-024-09822-w.
8
LncRNA 4930581F22Rik promotes myogenic differentiation by regulating the ERK/MAPK signaling pathway.长链非编码RNA 4930581F22Rik通过调节ERK/MAPK信号通路促进成肌分化。
Heliyon. 2024 May 6;10(9):e30640. doi: 10.1016/j.heliyon.2024.e30640. eCollection 2024 May 15.
9
Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway.GPX2 基因过表达通过 MAPK 信号通路调控猪前体脂肪细胞和骨骼肌细胞的发育。
PLoS One. 2024 May 9;19(5):e0298827. doi: 10.1371/journal.pone.0298827. eCollection 2024.
10
Natural products targeting the MAPK-signaling pathway in cancer: overview.天然产物靶向癌症中的 MAPK 信号通路：概述。
J Cancer Res Clin Oncol. 2024 Jan 9;150(1):6. doi: 10.1007/s00432-023-05572-7.
通过荧光激活细胞分选法分离骨骼肌干细胞。
Nat Protoc. 2015 Oct;10(10):1612-24. doi: 10.1038/nprot.2015.110. Epub 2015 Sep 24.
4
CLIP: viewing the RNA world from an RNA-protein interactome perspective.CLIP：从RNA-蛋白质相互作用组的角度审视RNA世界。
Sci China Life Sci. 2015 Jan;58(1):75-88. doi: 10.1007/s11427-014-4764-5. Epub 2015 Jan 10.
5
Regulation of microRNA function in somatic stem cell proliferation and differentiation.miRNA 在体干细胞增殖和分化中的功能调控。
Nat Rev Mol Cell Biol. 2014 Sep;15(9):565-76. doi: 10.1038/nrm3854. Epub 2014 Aug 13.
6
MicroRNA directly enhances mitochondrial translation during muscle differentiation.微小RNA在肌肉分化过程中直接增强线粒体翻译。
Cell. 2014 Jul 31;158(3):607-19. doi: 10.1016/j.cell.2014.05.047.
7
Gene regulatory networks and transcriptional mechanisms that control myogenesis.控制肌发生的基因调控网络和转录机制。
Dev Cell. 2014 Feb 10;28(3):225-38. doi: 10.1016/j.devcel.2013.12.020.
8
starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data.starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络。
Nucleic Acids Res. 2014 Jan;42(Database issue):D92-7. doi: 10.1093/nar/gkt1248. Epub 2013 Dec 1.
9
Oridonin induces apoptosis in SW1990 pancreatic cancer cells via p53- and caspase-dependent induction of p38 MAPK.冬凌草甲素通过 p53 和 caspase 依赖性诱导 p38 MAPK 诱导 SW1990 胰腺癌细胞凋亡。
Oncol Rep. 2014 Feb;31(2):975-82. doi: 10.3892/or.2013.2888. Epub 2013 Dec 2.
10
A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation.miR-133 与 ERK1/2 通路之间的反馈回路涉及调节成肌细胞增殖和分化的精细机制。
Cell Death Dis. 2013 Nov 28;4(11):e934. doi: 10.1038/cddis.2013.462.