CircSAMD4A aggravates H/R‐induced cardiomyocyte apoptosis and inflammatory response by sponging miR‐138‐5p

Hu, Xiaorong; Ma, Richard; Cao, Jinxin; Du, Xianjin; Cai, Xinyong; Fan, Yongzhen

doi:10.1111/jcmm.16093

Cited by 35 publications

(37 citation statements)

References 25 publications

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“…Evidence-Based Complementary and Alternative Medicine et al showed that miR-138-5p was downregulated in H9C2 cells after H/R treatment and miR-138-5p can promote H/Rinduced cardiomyocyte apoptosis and inflammation in vitro [19]. miR-16-5p is a miRNA located on human chromosome 3, which plays an important role in the process of cardiomyocyte apoptosis and cardiovascular formation [13].…”

Section: Discussionmentioning

confidence: 99%

“…Liu et al showed that inhibiting miR-101-3 p can inhibit the activation of the JAK2/STAT3 signaling pathway and downregulate the apoptosis of cardiomyocytes after H/R treatment [ 18 ]. And Hu et al showed that miR-138-5 p was downregulated in H9C2 cells after H/R treatment and miR-138-5 p can promote H/R-induced cardiomyocyte apoptosis and inflammation in vitro [ 19 ]. miR-16-5p is a miRNA located on human chromosome 3, which plays an important role in the process of cardiomyocyte apoptosis and cardiovascular formation [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

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miR-16-5p Regulates PTPN4 and Affects Cardiomyocyte Apoptosis and Autophagy Induced by Hypoxia/Reoxygenation

Cao

Liu

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objectives. To explore the effects of miR-16-5p and PTPN4 on the apoptosis and autophagy of AC16 cardiomyocytes after hypoxia/reoxygenation treatment. Methods. AC16 cells were divided into the control group (NC), hypoxia/reoxygenation group (H/R), knockdown miR-16-5p negative control group (NC inhibitor), knockdown miR-16-5p group (miR-16-5p inhibitor), overexpression miR-16-5p negative control group (NC mimics), overexpression miR-16-5p group (miR-16-5p mimics), silent PTPN4 negative control group (sh-NC), silent PTPN4 group (sh-PTPN4), and silent PTPN4 + knockdown miR-16-5p group (sh-PTPN4 + miR-16-5p inhibitor). Real-time fluorescent quantitative PCR (RT-qPCR) and western blotting (WB) were used to measure the expression level of miR-16-3p, miR-16-5p, protein tyrosine phosphatase nonreceptor type 4 (PTPN4), and autophagy-related proteins (beclin-1, LC3 II/I, and P26) in AC16 cells. The apoptosis level of AC16 cells in each group was measured by flow cytometry and TUNEL. The dual-luciferase reporter gene experiment was also used to verify the targeting relationship between miR-16-5p and PTPN4. Results. After H/R treatment, the levels of myocardial injury markers including LDH and CK-MB in AC16 cells were increased significantly ( P < 0.05 ), and the levels of cell apoptosis and autophagy also increased significantly ( P < 0.05 ). The level of miR-16-3p in AC16 cells did not change significantly after H/R treatment, whereas the level of miR-16-5p was increased significantly ( P < 0.05 ). After miR-16-5p was knocked down, the levels of LDH and CK-MB in AC16 cells treated with H/R were significantly reduced ( P < 0.05 ), and the rates of cell apoptosis and autophagy were also significantly reduced ( P < 0.05 ). miR-16-5p negatively regulated the expression level of PTPN4 protein in AC16 cells ( P < 0.05 ), and the dual-luciferase reporter gene experiment confirmed that PTPN4 was the downstream target of miR-16-5p. Silencing of PTPN4 significantly increased the damage of AC16 cells induced by H/R treatment ( P < 0.05 ), but simultaneously inhibiting the expression of PTPN4 and miR-16-5p reversed the protective effect of miR-16-5p knockdown on AC16 cells ( P < 0.05 ). Conclusions. The expression of miR-16-5p is upregulated in AC16 cells after H/R treatment and the knockdown which can protect AC16 cells from H/R-induced cell damage that may be due to its regulation on the expression of PTPN4.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR-16-5p Regulates PTPN4 and Affects Cardiomyocyte Apoptosis and Autophagy Induced by Hypoxia/Reoxygenation

Cao

Liu

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…For example, circRNA ITCH mediates H 2 O 2 -induced myocardial cell apoptosis by upregulating miR-17-5p via wnt/β-catenin signaling pathway (115). circSAMD4A aggravates hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and inflammatory response by sponging miR-138-5p (116).…”

Section: Circrna and Cvdsmentioning

confidence: 99%

Circular RNAs and Cardiovascular Regeneration

Tang

Jang

et al. 2021

Front. Cardiovasc. Med.

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circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.

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“…22 MiR-138-5p, as a member of miRNAs, is closely associated with various human diseases, including several types of cancers, [23][24][25] obesity, 26 and especially for inflammatory diseases. 27,28 Of inflammatory illnesses, miR-138-5p has been found downregulated in acute myocardial infarction model induced by hypoxia/reoxygenation 27 and chondrocytes of osteoarthritis model caused by IL-1β. 28 Conversely, miR-138-5p was overexpressed in pulmonary arterial smooth muscle cells/ lungs in patients or rats of pulmonary arterial hypertension, which could be alleviated by inhibiting the miR-138-5p expression.…”

Section: Introductionmentioning

confidence: 99%

“…10,14,[44][45][46] Accumulating evidence indicated the vital role of miR-138-5p in the development and homeostasis of the immune system. [23][24][25][26][27][28] In the majority, miR-138-5p seems to act as a tumor-suppressor miRNA by targeting specific oncogenic genes and is also being deregulated in cancer cells, such as glioma, 23 non-small cell lung cancer, 24 ovarian 47 and prostate cancer. 25 In the present study, low expression of miR-138-5p was found in the rat hippocampus of the cognitive impairment model and RM microglial cells stimulated with LPS.…”

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confidence: 99%

MicroRNA-138-5p Regulates Hippocampal Neuroinflammation and Cognitive Impairment by NLRP3/Caspase-1 Signaling Pathway in Rats

Feng

Zhan

et al. 2021

JIR

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Purpose Neuroinflammation is an essential causative factor in the pathogenesis and progression of cognitive impairment. The present study aims to evaluate the critical role of microRNA-138-5p (miR-138-5p) in hippocampal neuroinflammation and cognitive impairment through the NLRP3/caspase-1 signaling pathway in rats. Material and Methods We established the cognitive impairment rat model and RM (Rat microglia) microglial cellular inflammation model by intracerebroventricular (icv) injection or stimulation of lipopolysaccharide (LPS). Morris water maze (MWM) and Y-maze tests were performed to assess the cognitive behaviors. Quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-linked immune-sorbent assay (ELISA) and Western blot analysis were utilized to evaluate mRNA or protein expression. Bioinformatic analysis and dual-luciferase reporter gene assay were performed to verify the targeting relationship between NLRP3 and miR-138-5p. Besides, Hematoxylin and eosin (H&E) staining and immunohistochemistry were applied to observe the neuronal morphology and detect the positive cells of the hippocampus, respectively. Results Compared to the control groups, LPS-treated rats exhibited significantly impaired learning and memory in MWM and Y-maze tests. The expression of NLRP3, caspase-1 and pro-inflammation cytokines (IL-1β and IL-18) were upregulated, while miR-138-5p was downregulated both in rat hippocampus and RM cells treated with LPS. MiR-138-5p is downregulated in microarray data of cognitive impairment animals and could directly target the 3ʹ-UTR of NLRP3. Furthermore, upregulation of miR-138-5p improved impaired cognitive functions, while inhibited hippocampal neuroinflammation demonstrated by decreased expression of NLRP3/caspase-1 axis, pro-inflammation cytokines and microglial activation. This study demonstrates for the first time that miR-138-5p suppresses the hippocampal NLRP3/caspase-1 signaling pathway activation in cognition impaired rats. Conclusion The low expression of miR-138-5p after LPS administration may contribute to the activation of the NLRP3/caspase-1 pathway, leading to hippocampal neuroinflammation and cognitive impairment in rat models. These findings indicate a promising therapeutic avenue for cognitive disorders.

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CircSAMD4A aggravates H/R‐induced cardiomyocyte apoptosis and inflammatory response by sponging miR‐138‐5p

Cited by 35 publications

References 25 publications

miR-16-5p Regulates PTPN4 and Affects Cardiomyocyte Apoptosis and Autophagy Induced by Hypoxia/Reoxygenation

miR-16-5p Regulates PTPN4 and Affects Cardiomyocyte Apoptosis and Autophagy Induced by Hypoxia/Reoxygenation

Circular RNAs and Cardiovascular Regeneration

MicroRNA-138-5p Regulates Hippocampal Neuroinflammation and Cognitive Impairment by NLRP3/Caspase-1 Signaling Pathway in Rats

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