RISS 검색 - 국내학술지논문 상세보기

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다국어 초록 (Multilingual Abstract)

Background It is reported that LncRNAs play an important role in various diseases, including myocardial ischemia–reperfusion injury. However, the regulatory mechanism of LncRNAs in I/R injury of cardiac has not been fully elucidated.
Objective This study aimed to explore the interaction of LncRNA MALAT1 and aberrant histone modification in I/R injury cardiomyocytes.
Results After myocardial I/R or H/R injury, the expression level of CTCF was up-regulated and MALAT1 was downregulated.
Silencing of CTCF promoted the cardiomyocytes survival and apoptosis after H/R treatment. Moreover, the expression of H3K27me3 was significantly inhibited by CTCF down-regulation. H3K27me3 protein could directly bind to the promoter of MALAT1. In addition, we found that the inhibition CTCF could up-regulate the expression of MALAT1 in cardiomyocytes. In addition, down-regulation of MALAT1 could reverse the effects of silencing of CTCF on cardiomyocytes growth and apoptosis in H/R injury. Furthermore, the bioinformatic analysis showed 12 potential targets, while only miR- 26b-5p could directly bind with MALAT1. The inhibition of CTCF repressed the miR-26b-5p expression and the silencing of MALAT1 promoted miR-26b-5p expression. Besides, the miR-26b-5p was decreased in cardiomyocytes under H/R treatment.
Overexpression of MALAT1 significantly promoted cardiomyocytes cell growth and repressed cell apoptosis, while the miR-26b-5p reversed these effects. In myocardial I/R injury mice model, overexpression of MALAT1 alleviated the myocardial tissue injury and repressed the H3K27me3 level, however, all those effects were reversed by CTCF.
Conclusions CTCF was highly expressed in H/R cardiomyocytes and I/R myocardial tissue and the silencing of CTCFmediated H3K27me3 dissociating from the MALAT1 promoter to regulate cardiomyocytes survival and apoptosis by targeting miR-26b-5p. It provided a new therapeutic marker for myocardial I/R injury.