Effects of miR‑103a‑3p on the autophagy and apoptosis of cardiomyocytes by regulating Atg5

Zhang, Chenjun; Lu, Jianqiang; Wang, Hairong; Qi, Yuan; Kan, Ying; Zhang, Ge

doi:10.3892/ijmm.2019.4128

Cited by 21 publications

(23 citation statements)

References 54 publications

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“…Xiao et al (27) demonstrated that miR-24-3p decreased apoptosis in mouse cardiomyocytes in response to ischemia/reperfusion (I/R) injury. Zhang et al (2) also revealed that miR-103a-3p serves a protective role in myocardial I/R injury. Liu et al (28) demonstrated that miR-199a-5p expression affects hypoxia/reoxygenation-induced cytotoxicity in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 97%

“…Coronary heart disease is a major cause of death and disability that causes serious debilitation in patients, with an incidence rate that is increasing on a yearly basis (1,2). Acute myocardial infarction (MI) is a coronary heart disease with high worldwide incidence and mortality rates that leads to myocardial tissue injury and ultimately disability or death (3).…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

Sun

et al. 2020

Exp Ther Med

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In the present study, the role of microRNA-663b (miR-663b) in cardiomyocyte injury was examined. Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect miR-663b expression in hypoxia-induced H9c2 cells. The results revealed that miR-663b expression was significantly upregulated in hypoxia-induced H9c2 cells compared with control cells. TargetScan analysis and dual-luciferase reporter assays demonstrated that miR-663b directly targeted the B-cell lymphoma 2 like 1 (BCL2L1) gene. RT-qPCR and western blotting data indicated that BCL2L1 expression was significantly downregulated in hypoxia-induced H9c2 cells compared with control cells. Under hypoxic conditions, H9c2 cells were transfected with miR-663b inhibitor, inhibitor control, miR-663b inhibitor + control small interfering (si)RNA or miR-663b inhibitor + BCL2L1-siRNA for 48 h. ELISA against creatine kinase-muscle/brain (CK-MB) and cardiac troponin 1 (cTnI) demonstrated that the miR-663b inhibitor reduced CK-MD and cTnI release and increased mitochondrial viability when compared with hypoxia-treated cells. Additionally, the miR-663b inhibitor significantly increased H9c2 cell viability and decreased cell apoptosis under hypoxic conditions. The results of ELISA further revealed that the miR-663b inhibitor decreased the release of various inflammatory factors, including tumour necrosis factor α, interleukin (IL) 1β and IL-6 in H9c2 cells under hypoxic conditions. These changes were reversed following BCL2L1 knockdown. In conclusion, miR-663b inhibition protected cardiomyocytes against hypoxia-induced injury by targeting BCL2L1 and may potentially be a novel target for the treatment of patients with myocardial infarction.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

Sun

et al. 2020

Exp Ther Med

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“…In the in vitro studies, H/R treatment has been widely used to stimulate the cardiomyocytes and H/R treatment has been proven to induce myocardial apoptosis (Cheng et al, 2019; Huang et al, 2019; Yuan et al, 2019), and in our studies, we consistently showed that H/R treatment inhibited cell viability and induced cell apoptosis of HCMs. Using the in vitro model of H/R‐induced myocardial injury, the expression levels of various miRNAs such as miR‐340‐5p (Li, Zhou, Yang, & Yu, 2019), miR‐103a‐3p (C. Zhang et al, 2019), miR‐98 (Zhai et al, 2019), and miR‐148b‐3p (Sun et al, 2018) were significantly affected upon H/R stimulation in the cardiomyocytes, and restoring the levels of these miRNAs attenuated the H/R‐induced myocardial injury. In our study, we detected downregulation of miR‐885 in the H/R‐treated HCMs, suggesting the potential involvement of H/R‐induced HCM injury.…”

Section: Discussionmentioning

confidence: 99%

miR‐885 mediated cardioprotection against hypoxia/reoxygenation‐induced apoptosis in human cardiomyocytes via inhibition of PTEN and BCL2L11 and modulation of AKT/mTOR signaling

Meng

Mei

Zhao

et al. 2020

Journal Cellular Physiology

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Ischemia/reperfusion (I/R) injury could cause the enhanced cell apoptosis of cardiomyocytes, which is one of key contributors for the development of ischemic heart disease. Recent studies emphasized the role of microRNAs (miRNAs) in regulating cardiomyocyte apoptosis. The study planned to elucidate the molecular actions of miR‐885 on mediating human cardiomyocytes (HCMs) apoptosis induced by hypoxia/reoxygenation (H/R) and to explore the potential molecular mechanisms. The present data revealed that H/R stimulation inhibited HCM viability and potentiated HCM apoptosis, and more importantly, the expression of miR‐885 in HCMs was markedly repressed after H/R stimulation. Further experimental examinations demonstrated that overexpression of miR‐885 attenuated H/R‐induced increased in HCM apoptotic rates, while miR‐885 knockdown impaired HCM viability and increased HCM apoptotic rates. Moreover, the mechanistic studies showed that miR‐885 inversely regulated the expression of phosphatase and tensin homolog (PTEN) and BCL2 like 11 (BCL2L11) in HCMs, and enforced expression of PTEN and BCL2L11 partially antagonized the protective actions of miR‐885 overexpression on H/R‐induced HCM injury. Moreover, H/R suppressed AKT/mTOR signaling, which was attenuated by miR‐885 overexpression in HCMs. In conclusion, the present study for the first time showed the downregulation of miR‐885 induced by H/R in HCMs, and provided the evidence that miR‐885 attenuated H/R‐induced cell apoptosis via inhibiting PTEN and BLC2L11 and modulation of AKT/mTOR signaling in HCMs.

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“…As indicated from the reannotation analysis, NR_027324 was a segment of H9 gene, and mir-103-3p was evaluated as its binding target. MiR-103-3p could down regulate the protein expression of Beclin1, ATG5, and inhibit autophagy [11]. The authors inferred that NR_027324, a section of the H9 gene, may target miR-103-3p via CeRNA binding, adjust its expression, and subsequently regulate the downstream target gene ATG5 of miR-103-3p.…”

Section: Discussionmentioning

confidence: 99%

NR_027324 regulates autophagy and apoptosis by combining with miR-103-3p as ceRNA to regulate ATG5 in cardiomyocytes during hypoglycemic and hypoxic injury

Meng¹,

Tan²,

Gu³

et al. 2020

Preprint

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Background: Myocardial infarction (MI) refers to a fatal disease, and the border zone (BZ) of myocardial infarction is of high importance to the prognosis of myocardial infarction patients. Autophagy and apoptosis can significantly impact cardiovascular diseases. In the previous studies conducted by the authors, plenty of differential expressions of long non-coding RNA (lncRNA) were reported in the border zone of myocardial infarction. As revealed from the results of bioinformatics analysis, LncRNA may take up a vital part in the pathological process of cardiovascular disease by regulating apoptosis and autophagy. This study aimed to firstly conduct bioinformatics analyses to predict that NR_027324, as a competitive endogenous RNA (ceRNA), binds to miR-103-3p and subsequently regulates the expression of downstream target gene ATG5, to secondly verify the mentioned regulatory relationship by molecular biological experiments, and thirdly to investigate that the above pathways transmit apoptosis and autophagy signals in cardiomyocytes during hypoglycemic and anoxic injuries. Methods: The binding of NR_027324 to miR-103-3p was predicted by the bioinformatics analysis, and then the expression of downstream ATG5 was regulated. By the dual luciferase assay, the binding of NR_027324 to miR-103-3p was confirmed. H9c2 cells underwent the culture under low glucose and hypoxia to simulate cardiomyocytes under ischemia. NR_027324 siRNA and overexpression plasmid vector and miR-103-3p (mimics and inhibitors) were adopted to transfect cells to examine its function in cardiomyocytes. By the reverse transcription-quantitative polymerase chain reaction (RT-PCR), the expression levels of NR_027324, miR-103a-3p and ATG5 were assessed. Cell viability was measured by the MTT assay, and cell injury was analyzed by the lactate dehydrogenase assay (LDH). The western blotting assay was performed to detect the expressions of Bcl2, Bax, Atg5, cleaved-caspase3 and cleaved-caspase9. Moreover, the immunofluorescence assay was used to detect the expression of LC3-I/II as a marker of autophagy.Results: In hypoglycemic and anoxic H9C2 cells, the expressions of NR_027324 and ATG5 were up-regulated, while miR-103-3p showed a down-regulated expression. By the dual luciferase assay, the binding of NR_027324 to miR-103-3p was confirmed. The overexpressed NR_027324 could enhance the reduced cell viability of hypoglycemic and anoxic H9C2 cells and reduce cell damage. Interfering with the expression of NR_027324 could further reduce the viability of hypoglycemic anoxic H9C2 cells, increase injury, inhibit protective autophagy and accelerate apoptosis of hypoglycemic anoxic H9C2 cells. The mentioned pathophysiological processes were achieved by NR_027324 binding to miR-103-3p and then regulating the expression of target gene ATG5.Conclusion: In hypoglycemic and anoxic H9C2 cells, the expressions of NR_027324 and ATG5 are up-regulated, while the expression of miR-103-3p decreases. NR_027324 acts as ceRNA combined with miR-103-3p to regulate ATG5 and control autophagy and apoptosis in cardiomyocytes during hypoglycemic and anoxic injuries.

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Effects of miR‑103a‑3p on the autophagy and apoptosis of cardiomyocytes by regulating Atg5

Cited by 21 publications

References 54 publications

Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

Downregulation of miRNA‑663b protects against hypoxia‑induced injury in cardiomyocytes by targeting BCL2L1

miR‐885 mediated cardioprotection against hypoxia/reoxygenation‐induced apoptosis in human cardiomyocytes via inhibition of PTEN and BCL2L11 and modulation of AKT/mTOR signaling

NR_027324 regulates autophagy and apoptosis by combining with miR-103-3p as ceRNA to regulate ATG5 in cardiomyocytes during hypoglycemic and hypoxic injury

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