circ_0023461 Silencing Protects Cardiomyocytes from Hypoxia‐Induced Dysfunction through Targeting miR‐370‐3p/PDE4D Signaling

Abstract

Background. Acute myocardial infarction (AMI) is a common cardiovascular disease with high disability and mortality. Circular RNAs (circRNAs) are implicated in the pathomechanism of multiple human diseases, including AMI. This study intended to explore the function and working mechanism of a novel circRNA circ_0023461 in hypoxia-induced cardiomyocytes. Methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were implemented to detect RNA and protein expression. Cell counting kit-8 (CCK8) assay and 5-ethynyl-2 ′ -deoxyuridine (Edu) assay were conducted to analyze cell viability and proliferation ability. Cell migration and apoptosis were assessed by Transwell assay and flow cytometry. Cell oxidative stress was analyzed using the commercial kits. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze cell inflammation. Cell glycolytic metabolism was evaluated using the commercial kits. Dual-luciferase reporter assay and RNA pull-down assay were conducted to verify the intermolecular interactions. Results. circ_0023461 expression was upregulated in AMI patients and hypoxia-induced AC16 cells. Hypoxia restrained the viability, proliferation, migration, and glycolysis and induced the apoptosis, oxidative stress, and inflammation of AC16 cells, and these effects were attenuated by the silence of circ_0023461. MicroRNA-370-3p (miR-370-3p) was verified as a target of circ_0023461, and circ_0023461 silencing-mediated protective effects in hypoxia-induced cardiomyocytes were partly alleviated by the knockdown of miR-370-3p. miR-370-3p interacted with the 3 ′ untranslated region (3 ′ UTR) of phosphodiesterase 4D (PDE4D), and PDE4D overexpression partly reversed miR-370-3p overexpression-induced protective effects in hypoxia-induced cardiomyocytes. circ_0023461 can upregulate PDE4D expression by acting as a molecular sponge for miR-370-3p in AC16 cells. Conclusion. circ_0023461 knockdown attenuated hypoxia-induced dysfunction in AC16 cells partly by targeting the miR-370-3p/PDE4D axis.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

“…AC16 cells were transfected with small interfering RNAs (siRNAs) specific for S100A12 and nontargeting siRNAs (Shenggong, Shanghai, China) as a negative control (Si-NC) using Lipofectamine 3000 reagent (Invitrogen, Carlsbad, CA, USA). The transfection time was 48 hours, and the concentration of siRNAs used was 50 nM [ 29 ]. In addition, S100A12 overexpression and negative control overexpression (OE-NC) plasmids (3 μ g) were transfected into AC16 cells.…”

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

“…Hypoxia induces adaptive response to maintain the homeostasis of intracellular environment and promote cell survival (Kong et al 2022 ; Qureshi-Baig et al 2020 ). For others, hypoxia induces cell death by activating apoptosis (Ren et al 2021 ; Mueller-Buehl et al 2021 ). The research on the changes of metabolic function caused by hypoxia and its mechanism will help to understand the pathogenesis of hypoxic diseases.…”

Coevolution of Rumen Epithelial circRNAs with Their Microbiota and Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep

“…Ding et al found that circ_0010283 regulated the viability and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein by targeting miR-370-3p [ 43 ]. Ren et al found that circ_0023461 protected cardiomyocytes from hypoxia-induced dysfunction by targeting miR-370-3p [ 44 ]. In this study, DE circRNA NC_040269.1:68309959|68364662 could target miR-150 and miR-370-3p, Oar-miR-370-3p inhibited fat accumulation, which might result from the inhibition of saturated fatty acids that promoted the accumulation of polyunsaturated fatty acids [ 45 ].…”