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LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy.
Theranostics ( IF 12.4 ) Pub Date : 2019-01-01 , DOI: 10.7150/thno.31052 Yu Feng 1, 2 , Weiting Xu 3 , Wei Zhang 3 , Wenjing Wang 3 , Tong Liu 2 , Xiang Zhou 3
Theranostics ( IF 12.4 ) Pub Date : 2019-01-01 , DOI: 10.7150/thno.31052 Yu Feng 1, 2 , Weiting Xu 3 , Wei Zhang 3 , Wenjing Wang 3 , Tong Liu 2 , Xiang Zhou 3
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Background: We generated a rat model of diabetic cardiomyopathy (DCM) and reported significant upregulation of the long non-coding RNA DCRF. This study was designed to determine the molecular mechanisms of DCRF in the development of DCM. Methods: Real-time PCR and RNA fluorescent in situ hybridization were conducted to detect the expression pattern of DCRF in cardiomyocytes. Histological and echocardiographic analyses were used to assess the effect of DCRF knockdown on cardiac structure and function in diabetic rats. mRFP-GFP-LC3 fluorescence microscopy, transmission electron microscopy, and Western blotting were carried out to determine cardiomyocyte autophagy. RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the regulatory role of DCRF/miR-551b-5p/PCDH17 pathway in cardiomyocyte autophagy. Results: Our findings showed that DCRF knockdown reduced cardiomyocyte autophagy, attenuated myocardial fibrosis, and improved cardiac function in diabetic rats. High glucose increased DCRF expression and induced autophagy in cardiomyocytes. RNA immunoprecipitation and luciferase reporter assays indicated that DCRF was targeted by miR-551b-5p in an AGO2-dependent manner and PCDH17 was the direct target of miR-551b-5p. Forced expression of DCRF was found to attenuate the inhibitory effect of miR-551b-5p on PCDH17. Furthermore, DCRF knockdown decreased PCDH17 expression and suppressed autophagy in cardiomyocytes treated with high glucose. Conclusion: Our study suggests that DCRF can act as a competing endogenous RNA to increase PCDH17 expression by sponging miR-551b-5p, thus contributing to increased cardiomyocyte autophagy in DCM.
中文翻译：
LncRNA DCRF通过将miR-551b-5p靶向糖尿病性心肌病来调节心肌细胞的自噬。
背景：我们生成了糖尿病性心肌病（DCM）的大鼠模型，并报告了长期的非编码RNA DCRF的显着上调。本研究旨在确定DCRF在DCM发生过程中的分子机制。方法：采用实时荧光定量PCR和RNA荧光原位杂交技术检测DCRF在心肌细胞中的表达模式。使用组织学和超声心动图分析来评估DCRF敲低对糖尿病大鼠心脏结构和功能的影响。进行了mRFP-GFP-LC3荧光显微镜检查，透射电子显微镜检查和蛋白质印迹分析，以确定心肌细胞的自噬。进行了RNA免疫沉淀和荧光素酶报告基因分析，以阐明DCRF / miR-551b-5p / PCDH17通路在心肌细胞自噬中的调节作用。结果：我们的研究结果表明，DCRF抑制可减少糖尿病大鼠的心肌自噬，减弱心肌纤维化和改善心脏功能。高葡萄糖可增加心肌细胞中DCRF的表达并诱导自噬。RNA免疫沉淀和荧光素酶报告基因检测表明，miR-551b-5p以AGO2依赖性方式靶向DCRF，而PCDH17是miR-551b-5p的直接靶标。发现DCRF的强制表达减弱了miR-551b-5p对PCDH17的抑制作用。此外，DCRF敲低降低了高糖治疗的心肌细胞中PCDH17的表达并抑制了自噬。结论：我们的研究表明DCRF可以作为海绵状miR-551b-5p的竞争性内源RNA来增加PCDH17的表达，从而促进DCM中心肌细胞自噬的增加。
更新日期：2019-01-01
中文翻译：
LncRNA DCRF通过将miR-551b-5p靶向糖尿病性心肌病来调节心肌细胞的自噬。
背景：我们生成了糖尿病性心肌病（DCM）的大鼠模型，并报告了长期的非编码RNA DCRF的显着上调。本研究旨在确定DCRF在DCM发生过程中的分子机制。方法：采用实时荧光定量PCR和RNA荧光原位杂交技术检测DCRF在心肌细胞中的表达模式。使用组织学和超声心动图分析来评估DCRF敲低对糖尿病大鼠心脏结构和功能的影响。进行了mRFP-GFP-LC3荧光显微镜检查，透射电子显微镜检查和蛋白质印迹分析，以确定心肌细胞的自噬。进行了RNA免疫沉淀和荧光素酶报告基因分析，以阐明DCRF / miR-551b-5p / PCDH17通路在心肌细胞自噬中的调节作用。结果：我们的研究结果表明，DCRF抑制可减少糖尿病大鼠的心肌自噬，减弱心肌纤维化和改善心脏功能。高葡萄糖可增加心肌细胞中DCRF的表达并诱导自噬。RNA免疫沉淀和荧光素酶报告基因检测表明，miR-551b-5p以AGO2依赖性方式靶向DCRF，而PCDH17是miR-551b-5p的直接靶标。发现DCRF的强制表达减弱了miR-551b-5p对PCDH17的抑制作用。此外，DCRF敲低降低了高糖治疗的心肌细胞中PCDH17的表达并抑制了自噬。结论：我们的研究表明DCRF可以作为海绵状miR-551b-5p的竞争性内源RNA来增加PCDH17的表达，从而促进DCM中心肌细胞自噬的增加。
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