Exosomes derived from the blood of patients with sepsis regulate apoptosis and aerobic glycolysis in human myocardial cells via the hsa‑miR‑1262/SLC2A1 signaling pathway

Sun,Fangyuan; Geng,Huan; Sun,Yuxia; Feng,Wentao; Tian,Tianning; Ye,Liang; Lei,Ming

doi:10.3892/mmr.2022.12635

Exosomes derived from the blood of patients with sepsis regulate apoptosis and aerobic glycolysis in human myocardial cells via the hsa‑miR‑1262/SLC2A1 signaling pathway

Authors:
- Fangyuan Sun
- Huan Geng
- Yuxia Sun
- Wentao Feng
- Tianning Tian
- Liang Ye
- Ming Lei
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Affiliations: Trauma Emergency Center, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
Published online on: February 8, 2022 https://doi.org/10.3892/mmr.2022.12635
Article Number: 119

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Abstract

Myocardial injury occurs in the majority of patients with sepsis and is associated with early mortality. MicroRNAs (miRs) transported by exosomes have been implicated in numerous diseases, such as tumors, acute myocardial infarction and cardiovascular disease. Human serum albumin (hsa)‑miR‑1262 has been shown to serve a role in sepsis; however, its role in exosomes isolated from patients with sepsis and septic myocardial injury remains unclear. In the present study, serum exosomes were isolated via ultracentrifugation. Solute carrier family 2 member 1 (SLC2A1), an essential mediator in energy metabolism, was silenced and overexpressed in the human myocardial AC16 cell line using lentiviral plasmids containing either SLC2A1‑targeting short interfering RNAs or SLC2A1 cDNA, respectively. Cell apoptosis was analyzed using flow cytometry, and the extracellular acidification rate and oxygen consumption rate of AC16 cells were determined using an XFe24 Extracellular Flux Analyzer. Furthermore, the dual‑luciferase reporter assay was used to evaluate the interaction between hsa‑miR‑1262 and SLC2A1. Finally, reverse transcription‑quantitative PCR and western blotting were used to evaluate gene and protein expression levels, respectively. Exosomes isolated from the blood of patients with sepsis (Sepsis‑exo) markedly reduced aerobic glycolysis activity, but significantly promoted the apoptosis of human AC16 cells in a time‑dependent manner. Moreover, Sepsis‑exo significantly increased hsa‑miR‑1262 expression levels, but significantly decreased SLC2A1 mRNA expression levels in a time‑dependent manner. Bioinformatics analysis indicated that hsa‑miR‑1262 bound to the 3' untranslated region of SLC2A1 to negatively regulate its expression. The silencing of SLC2A1 promoted apoptosis and suppressed glycolysis in AC16 cells, whereas SLC2A1 overexpression resulted in the opposite effects. Therefore, the present study demonstrated that exosomes derived from patients with sepsis may inhibit glycolysis and promote the apoptosis of human myocardial cells through exosomal hsa‑miR‑1262 via its target SLC2A1. These findings highlighted the importance of the hsa‑miR‑1262/SLC2A1 signaling pathway in septic myocardial injury and provided novel insights into therapeutic strategies for septic myocardial depression.

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