Suppression of long noncoding RNA NEAT1 attenuates hypoxia-induced cardiomyocytes injury by targeting miR-378a-3p.

lncRNA NEAT1 is involved in the development of many diseases. However, the function of lncRNA NEAT1 in myocardial infarction is unclear. Therefore, this experimental design based on lncRNA NEAT1 to explore the pathogenesis of myocardial infarction. RT-qPCR was used to detect the expression of lncRNA NEAT1 and miR-378a-3p in peripheral blood and mouse cardiomyocytes of patients with myocardial infarction. MTT assay, flow cytometry, Caspase-3 kit and transwell assay were used to detect the effects of lncRNA NEAT1 and miR-378a-3p on cardiomyocyte proliferation, apoptosis and migration. Target gene prediction and screening, luciferase reporter assays were used to verify downstream target genes for lncRNA NEAT1 and miR-378a-3p. Western blotting was used to detect the protein expression of Atg12 and related autophagy genes. lncRNA NEAT1 was highly expressed in peripheral blood and mouse cardiomyocytes of patients with myocardial infarction. Moreover, lncRNA NEAT1 significantly promoted cell proliferation and migration of cardiomyocytes. In addition, lncRNA NEAT1 inhibited miR-378a-3p expression, and miR-378a-3p inhibited Atg12 expression, while lncRNA NEAT1 regulated expression of Atg12 and related autophagic factors via miR-378a-3p. Knockout of microRNA-378-3p reversed the effects of NEAT1 silencing on cell damage. lncRNA NEAT1 can regulate the proliferation of cardiomyocytes by regulating miR-378-3p/Atg12 axis, thus accelerating the occurrence and development of cardiomyocytes.

Zhao J ，Chen F ，Ma W ，Zhang P ... -  《-》

Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR-204-3p and inhibiting autophagy.

This study was aimed at investigating the effects of lncRNA AK139328 on myocardial ischaemia/reperfusion injury (MIRI) in diabetic mice. Ischaemia/reperfusion (I/R) model was constructed in normal mice (NM) and diabetic mice (DM). Microarray analysis was utilized to identify lncRNA AK139328 overexpressed in DM after myocardial ischaemia/reperfusion (MI/R). RT-qPCR assay was utilized to investigate the expressions of lncRNA AK139328 and miR-204-3p in cardiomyocyte and tissues. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening (FS) were obtained by transthoracic echocardiography. Haematoxylin-eosin (HE) staining and Masson staining were utilized to detect the damage of myocardial tissues degradation of myocardial fibres and integrity of myocardial collagen fibres. Evans Blue/TTC staining was used to determine the myocardial infarct size. TUNEL staining was utilized to investigate cardiomyocyte apoptosis. The targeted relationship between lncRNA AK139328 and miR-204-3p was confirmed by dual-luciferase reporter gene assay. MTT assay was used for analysis of cardiomyocyte proliferation. Western blot was utilized to investigate the expression of alpha smooth muscle actin (α-SMA), Atg7, Atg5, LC3-II/LC3-I and p62 marking autophagy. Knockdown of lncRNA AK139328 relieved myocardial ischaemia/reperfusion injury in DM and inhibited cardiomyocyte autophagy as well as apoptosis of DM. LncRNA AK139328 modulated miR-204-3p directly. MiR-204-3p and knockdown of lncRNA AK139328 relieved hypoxia/reoxygenation injury via inhibiting cardiomyocyte autophagy. Silencing lncRNA AK139328 significantly increased miR-204-3p expression and inhibited cardiomyocyte autophagy, thereby attenuating MIRI in DM.

Yu SY ，Dong B ，Fang ZF ，Hu XQ ，Tang L ，Zhou SH ... -  《-》

Inhibition of lncRNA TUG1 upregulates miR-142-3p to ameliorate myocardial injury during ischemia and reperfusion via targeting HMGB1- and Rac1-induced autophagy.

Su Q ，Liu Y ，Lv XW ，Ye ZL ，Sun YH ，Kong BH ，Qin ZB ... -  《-》

LncRNA XIST promotes myocardial infarction by regulating FOS through targeting miR-101a-3p.

Lin B ，Xu J ，Wang F ，Wang J ，Zhao H ，Feng D ... -  《Aging-US》

Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats.

This study aimed to investigate the effects of long non-coding RNA (lncRNA)-nuclear-enriched abundant transcript (Neat1) on myocardial ischemia reperfusion injury in diabetic rats ex vivo and in vivo. Screening for LncRNA Neat1 expression was performed in rat myocardial tissues using microarray analysis and verified by qRT-PCR. Cell viability of rat cardiomyocytes was analyzed by MTT assay. Levels of autophagy-related proteins Atg7, Atg5, LC3-II/LC3-I and p62 were determined by Western blot assay. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening were obtained by transthoracic echocardiography. Left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), maximum rate of increase or decrease of left ventricular pressure (±dp/dtmax) and heart rate were obtained by computer algorithms and an interactive videographics programme. Myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride (TTC) staining. Myocardial apoptotic index was analyzed by TUNEL assay and immunohistochemical staining. Autophagic flux was examined by evaluating fluorescent LC3 puncta. Neat1 was highly expressed in ischemia reperfusion-treated diabetic rat myocardial tissues. Overexpression of Neat1 promoted the production of lactate dehydrogenase, inhibited superoxide dismutase content and cardiomyocyte viability. Neat1 overexpression also promoted the production of serum myocardial enzymes, including creatine kinase and creatine kinase-MB, and increased infarct size. By promoting myocardial apoptosis and autophagy, Neat1 aggravated myocardial ischemia reperfusion (I/R) injury in diabetic rats. Neat1 promoted cardiomyocyte autophagy by up-regulating Foxo1 expression to increase hypoxia-reoxygenation injury. I/R treatment caused more injuries in diabetic rats compared with normal rats. Elevated Neat1 expression aggravates myocardial ischemia reperfusion injury via activation of apoptosis and autophagy in diabetic rats. Foxo1 is one of the molecular mechanisms underlying Neat1-induced autophagy.

Ma M ，Hui J ，Zhang QY ，Zhu Y ，He Y ，Liu XJ ... -  《-》