首页|丙酮酸激酶同工酶M2介导长非编码RNA RP11-879F14.2发挥抑制心肌细胞肥大作用

丙酮酸激酶同工酶M2介导长非编码RNA RP11-879F14.2发挥抑制心肌细胞肥大作用

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越来越多的证据表明,长非编码RNA(lncRNA)在生物学功能调节中发挥着重要的作用.实时定量PCR(RT-qPCR)检测显示,与健康器官捐献者(n=23)相比,长非编码RNARP11-879F14.2在心力衰竭(heart failure,HF)患者(n=21)心肌中表达水平显著升高,但其在心肌肥厚调节中可能的作用和机制尚不清楚.利用腺病毒介导在乳小鼠心肌细胞(neonatal mouse ventricular cardiomyocytes,NMVCs)和乳大鼠心肌细胞(neonatal rat ventricular cardiomyocytes,NRVCs)中过表达RP11-879F14.2,检测对NMVCs中心肌肥厚相关基因,包括肌球蛋白重链(MYH7)、骨骼肌肌动蛋白(Acta1)以及心钠素(NPPA)表达的影响,结果显示,过表达RP11-879F14.2可显著抑制NMVCs和NRVCs中心肌肥厚相关基因表达.RT-qPCR和Western印迹结果证实,当过表达RP11-879F14.2时可显著促进NMVCs中丙酮酸激酶同工酶M2(PKM2)表达.并且,过表达PKM2和RP11-879F14.2可一致地抑制NMVCs和NRVCs中心肌肥厚相关基因表达和去氧肾上腺素(phenylephrine,PE)诱导NRVCs的表面积增加,而敲降PKM2可逆转RP11-879F14.2对NMVCs中心肌肥厚相关基因表达的抑制作用.利用Seahorse 96XF细胞能量分析仪检测显示,过表达RP11-879F14.2和PKM2可一致增加NMVCs中葡萄糖代谢水平,而沉默PKM2对RP11-879F14.2上调NMVCs中糖酵解、三羧酸(TCA)循环和线粒体电子传递链(ETC)相关基因的表达有显著的抑制作用.因此,PKM2介导RP11-879F14.2发挥抑制心肌细胞肥大的作用.
Long Non-coding RNA RP11-879F14.2 Inhibits Cardiomyocyte Hypertrophy via Upregulating PKM2 Expression
The increasing evidence suggests that long noncoding RNAs play an important role in regulating biological functions.Comparing with the healthy organ donors(n=23),the results of real-time quantitative polymerase chain reaction(RT-qPCR)assay showed that long noncoding RNA RP11-879F14.2 was significantly increased in the myocardium of patients with heart failure(HF)(n=21),however,the role and mechanism of RP11-879F14.2 in cardiac hypertrophy remains unclear.The effect of adenovirus-mediated overexpression of RP11-879F14.2 on the expression of hypertrophy-related genes,including myosin heavy chain 7(MYH7),skeletal muscle actin alpha 1(ACTA1)and natriuretic peptide type A(NPPA),was evaluated,and the RT-qPCR results revealed that overexpression of RP11-879F14.2 could markedly inhibit the expression of cardiac hypertrophy-related genes in neonatal mouse ventricular cardiomyocytes(NMVCs)and neonatal rat ventricular cardiomyocytes(NRVCs).The results of RT-qPCR and Western blotting showed that RP11-879F14.2 could efficiently enhance the expression of pyruvate kinase M2(PKM2)in NMVCs.Overexpression of PKM2 and RP11-879F14.2 could consistently attenuate the hypertrophy-related genes expression in NMVCs and NRVCs,and inhibited the increase of cell size of phenylephrine(PE)-induced NRVCs.Moreover,knock-down of PKM2 could reverse the inhibitory effect of RP11-879F14.2 on the cardiac hypertrophy-related genes expression in NMVCs.The glucose metabolic alterations were accessed by using Seahorse XF96 extracellular flux analyzer.Overexpression of RP11-879F14.2 and PKM2 could consistently enhance glucose metabolism in NMVCs,but knock-down of PKM2 could inhibit some RP11-879F14.2-promoted glycolysis-related genes,TCA cycle-related genes and mitochondrial ETC-related genes expression in NMVCs.Therefore,RP11-879F14.2 inhibits cardiomyocyte hypertrophy via upregulating PKM2 expression.

cardiac hypertrophycardiomyocytelong non-coding RNA(LncRNA)pyruvate kinase M2(PKM2)

李艺、温艺红、伍华燕、姜佳雪、欧涛、陈凯茵、刘宇鹏、单志新

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南方医科大学附属广东省人民医院(广东省医学科学院)医学研究部广东省临床药理学重点实验室,广州 510080

华南理工大学医学院,广州 510006

南方医科大学附属广东省人民医院(广东省医学科学院)心内科,广州 510080

心肌肥厚 心肌细胞 长非编码RNA 丙酮酸激酶同工酶M2

国家自然科学基金国家自然科学基金国家自然科学基金广东省自然科学基金广东省自然科学基金广东省自然科学基金广东省自然科学基金广东省自然科学基金广州市基础与应用基础研究项目广东省人民医院国自然培育项目

8207025482200325823002772022A15150125222022A15150121752021A15152201222023A15150102012021A1515111173202201011627KY0120220028

2024

10.13865/j.cnki.cjbmb.2024.02.1002

中国生物化学与分子生物学报
中国生物化学与分子生物学会 北京大学

中国生物化学与分子生物学报

CSTPCD北大核心
影响因子：0.617
ISSN：1007-7626
年,卷(期)：2024.40(4)
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