Dataset Information

Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression.

ABSTRACT: The immature phenotype of embryonic stem cell-derived cardiomyocytes (ESC-CMs) limits their application. However, the molecular mechanisms of cardiomyocyte maturation remain largely unexplored. This study found that overexpression of long noncoding RNA (lncRNA)-Cmarr, which was highly expressed in cardiomyocytes, promoted the maturation change and physiological maturation of mouse ESC-CMs (mESC-CMs). Moreover, transplantation of cardiac patch overexpressing Cmarr exhibited better retention of mESC-CMs, reduced infarct area by enhancing vascular density in the host heart, and improved cardiac function in mice after myocardial infarction. Mechanism studies identified that Cmarr acted as a competitive endogenous RNA to impede the repression of miR-540-3p on Dtna expression and promoted the binding of the dystrophin-glycoprotein complex (DGC) and yes-associated protein (YAP), which in turn reduced the proportion of nuclear YAP and the expression of YAP target genes. Therefore, this study revealed the function and mechanism of Cmarr in promoting cardiomyocyte maturation and provided a lncRNA that can be used as a functional factor in the construction of cardiac patches for the treatment of myocardial infarction.

SUBMITTER: Wu Y

PROVIDER: S-EPMC9382425 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression.

Wu Yukang Y Guo Xudong X Han Tong T Feng Ke K Zhang Peng P Xu Yanxin Y Yang Yiwei Y Xia Yuchen Y Chen Yang Y Xi Jiajie J Yang Huangtian H Wan Xiaoping X Kang Jiuhong J

Molecular therapy. Nucleic acids 20220731

The immature phenotype of embryonic stem cell-derived cardiomyocytes (ESC-CMs) limits their application. However, the molecular mechanisms of cardiomyocyte maturation remain largely unexplored. This study found that overexpression of long noncoding RNA (lncRNA)-Cmarr, which was highly expressed in cardiomyocytes, promoted the maturation change and physiological maturation of mouse ESC-CMs (mESC-CMs). Moreover, transplantation of cardiac patch overexpressing Cmarr exhibited better retention of mE ...[more]

PMID: 36035750

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Project description:BackgroundColorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.MethodsCRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.ResultsOur study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.ConclusionOur study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

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Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression.

Publications

Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression.

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