Research paperSuppression of long noncoding RNA NEAT1 attenuates hypoxia-induced cardiomyocytes injury by targeting miR-378a-3p
Introduction
Cardiovascular disease is a common and frequently-occurring disease, and it is one of the most important diseases that threaten human health today (Levin, 2010, Levin, 2010, Levin, 2010, Thavendiranathan et al., 2006, Thavendiranathan et al., 2006, Thavendiranathan et al., 2006). Both morbidity and mortality are among the top of all diseases (Danesh et al., 2005, Danesh et al., 2005, Danesh et al., 2005). In recent years, with the development of medicine and scientific and technological progress, basic research on cardiovascular diseases has made great progress, and the understanding of diseases has been deepened from the overall and organizational levels to the level of cells and molecules, so some new theories and new technologies have emerged (Alpert, 2004, Alpert, 2004, Alpert, 2004, Vaina and Serruys, 2006, Vaina and Serruys, 2006, Vaina and Serruys, 2006). Studying the pathophysiological mechanism of myocardial injury in cardiovascular disease and finding effective prevention and treatment drugs has become a research hotspot. Cardiomyocyte damage includes cell necrosis and apoptosis (Bao et al., 2014, Bao et al., 2014, Bao et al., 2014). Myocardial ischemia/reperfusion in acute myocardial infarction (AMI) is one of the most common pathophysiological processes of myocardial injury in the clinic. A large number of studies have confirmed that there is not only necrosis of cardiacmyocytes, but also apoptosis of cardiacmyocytes (Naaijkens et al., 2014, Naaijkens et al., 2014, Naaijkens et al., 2014). It has been found that apoptosis is the main form of myocardial damage, and cell necrosis is followed (Rajtik et al., 2016, Rajtik et al., 2016, Rajtik et al., 2016). In addition, cardiomyocyte apoptosis in the peripheral region of the infarct enlarges the infarct size, promotes ventricular remodeling, and adversely affects the myocardium. Therefore, reducing the necrosis and apoptosis of cardiomyocytes caused by injury is of great significance for prevention and treatment of myocardial I/R injury, perioperative myocardial protection and recovery of cardiac function.
At present, a lot of researches have been carried out on the pathogenesis of cardiovascular diseases from epidemiology, pathophysiology and molecular biology. More and more research has found that non-coding RNA also plays a crucial role. As an important part of the non-coding RNA family, the mechanism of long non-coding RNA (lncRNA) participating in the regulation of cardiovascular diseases is a hotspot in this field (Krystal et al., 2015, Krystal et al., 2015, Krystal et al., 2015, Uchida and Dimmeler, 2015, Uchida and Dimmeler, 2015, Uchida and Dimmeler, 2015). Lnc RNA refers to a class of non-coding RNA molecules with a transcript of more than 200 nucleotides in length located in the nucleus or cytoplasm (Yang et al., 2014, Yang et al., 2014, Yang et al., 2014). Study has shown that a series of lnc RNAs are involved in the development of the heart (Grote et al., 2013, Grote et al., 2013, Grote et al., 2013). NEAT1 is a newly discovered lnc RNA in recent years. Initial studies have found that NEAT1 is involved in regulating gene expression mainly by stabilizing the RNA in the nucleus. In recent years, more and more studies have found that NEAT1 plays an important role in the occurrence and development of diseases. The study has found that lnc RNA NEAT1 is one of the differential proteins between gastric cancers and normal tissues, they also found that the high expression of NEAT1 was closely related to the high clinical stage and lymph node metastasis of gastric cancer (Chai et al., 2016, Chai et al., 2016, Chai et al., 2016, Chakravarty et al., 2014, Chakravarty et al., 2014, Chakravarty et al., 2014). However, little is known about the role of lnc RNA NEAT1 in the cardiovascular system. The function and mechanism of action of lncRNA NEAT1 are not fully understood. Therefore, it is necessary to study the mechanism of lnc RNA NEAT1 in the cardiovascular system.
There is a mutual regulation between long-chain non-coding RNA (lncRNA) and microRNA (miRNA) (Ye et al., 2014, Ye et al., 2014, Ye et al., 2014). lncRNA can interact with miRNA as a competitive endogenous RNA (ceRNA) and participate in the regulation of target gene expression. It has been found that lnc RNA NEAT1 negatively regulates the expression of mir-132 in glioma, while mir-132 targeting Sox 2 down-regulates the expression of mir-132. lnc RNA NEAT1 promotes the development of glioma by inhibiting mir-132 expression. Conversely, miRNA can play a biological role through RNA-induced silencing complex (RISC) regulation of lncRNA (Ballantyne et al., 2016, Ballantyne et al., 2016, Ballantyne et al., 2016, Paraskevopoulou and Hatzigeorgiou, 2016, Paraskevopoulou and Hatzigeorgiou, 2016, Paraskevopoulou and Hatzigeorgiou, 2016). Numerous studies have shown that miRNA play a crucial role in the pathogenesis of a variety of cardiovascular diseases, including myocardial infarction, cardiac stem cells, myocardial ischemia–reperfusion injury, cardiac development, myocardial remodeling, arrhythmia, heart failure, congenital heart disease, etc (Cao et al., 2016, Cao et al., 2016, Cao et al., 2016, Jones Buie et al., 2016, Jones Buie et al., 2016, Jones Buie et al., 2016). miR-378a-3p is an important member in miRNAs, and it is involved in regulating the occurrence and development of various diseases (Huang et al., 2015, Huang et al., 2015, Huang et al., 2015, Ikeda et al., 2015, Ikeda et al., 2015, Ikeda et al., 2015). However, it is still necessary to further explore the mechanism to fully reveal its mechanism. Therefore, it is meaningful to analyze the role of lncRNA-mi RNA network correlation in the pathogenesis of myocardial injury.
In view of the above problems, this study intends to detect the expression of lncRNA NEAT1 in peripheral blood and cells of patients with myocardial infarction, explore the effect of lncRNA NEAT1 expression on the proliferation and migration of myocardial cells, explore the effect of lncRNA NEAT1 on the biological behavior of myocardial cells through microRNA-378a-3p, and provide reliable basis for clinical diagnosis and targeted therapy of myocardial infarction.
Section snippets
Patients
A total of 80 patients who underwent coronary angiography to assess chest pain were enrolled in hospitalized patients admitted to Shandong Provincial Hospital affiliated to Shandong University. A retrospective analysis of the patient's angiogram was performed by two independent cardiologists. The study was approved by the Ethics Committee of Shandong Provincial Hospital affiliated to Shandong University, and all patients signed informed consent.
Cell culture and treatment
Detailed methods of myocyte isolation are
Up-regulated NEAT1 were associated with hypoxia cardiomyocytes
As shown in Fig. 1A, NEAT1 was significantly up-regulated in peripheral blood of patients with unstable angina and patients with ischemic cardiomyopathy/myocardial infarction (MI) compared with that in the control patients. And as shown in SFig1A, MALAT1was significantly up-regulated in peripheral blood of patients with unstable angina and patients with ischemic cardiomyopathy/myocardial infarction (MI) compared with that in the control patients.
It was found that the level of NEAT1 increased
Discussion
Myocardial infarction is a cardiovascular disease with a high incidence and mortality caused by multiple factors and multiple factors (Jenkins et al., 2017, Jenkins et al., 2017, Jenkins et al., 2017). It has been reported that acute ischemia and hypoxia of the myocardium can cause obvious morphological changes in cardiomyocytes, eventually leading to apoptosis or necrosis of cardiomyocytes (Harada et al., 2005, Harada et al., 2005, Harada et al., 2005). Ischemia and hypoxia are the
Conclusion
NEAT1 affects the proliferation and invasion and metastasis of cardiomyocytes by regulating the expression of miR-378-3p/Atg7 axis, suggesting that NEAT1 may be a potential therapeutic target for myocardial infarction. It provides experimental basis for the clinical prognosis of the disease and further intervention treatment research.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Not applicable.
Funding
Not applicable.
Ethics approval and consent to participate
The present study was approved by the Ethics Committee of Shandong Provincial Hospital affiliated to Shandong University. The research has been carried out in accordance with the World Medical Association Declaration of Helsinki. All patients and healthy volunteers provided written informed consent prior to their inclusion within the study.
Consent for publication
All authors have read and approved the final manuscript.
Authors contribution
Jiali Zhao, Fudi Chen, Peng Zhang designed and carried out the study. Jiali Zhao, Fudi Chen and Wei Ma participated in experiments and statistical analysis. Jiali Zhao, Fudi Chen wrote the manuscript. Peng Zhang revised the manuscript. All authors read and approved the final manuscript.
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