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The Essential Function of miR-5739 in Embryonic Muscle Development

  • Ji-Heon Lee (R&D Center, CLECELL Inc.) ;
  • Min Sup Kim (R&D Center, CLECELL Inc.) ;
  • Jin-seop Lee (R&D Center, CLECELL Inc.) ;
  • Dong Hyun Lee (R&D Center, CLECELL Inc.) ;
  • Chansol Park (R&D Center, CLECELL Inc.) ;
  • Dong Hyuk Lee (R&D Center, CLECELL Inc.) ;
  • Eun-Young Kim (Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University) ;
  • Hyung Min Chung (Mirae Cell Bio Inc.)
  • Received : 2022.11.11
  • Accepted : 2022.11.29
  • Published : 2023.05.30

Abstract

Background and Objectives: Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. Methods and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3' untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. Conclusions: Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regulate muscle and vascular differentiation during embryonic development.

Keywords

Acknowledgement

This work was supported by a grant (715003-07) from the Research Center for Production Management and Technical Development for High Quality Livestock Products through Agriculture, Food and Rural Affairs Convergence Technologies Program for Educating Creative Global Leader, Ministry of Agriculture, Food and Rural Affairs.

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