Overexpression of miR‑17‑5p protects against high glucose‑induced endothelial cell injury by targeting E2F1‑mediated suppression of autophagy and promotion of apoptosis

Abstract

E2 promoter binding factor 1 (E2F1) has been reported to have an important regulatory role in cell survival during hyperglycemic conditions; however, the mechanisms remain to be fully elucidated. Bioinformatics analyses have suggested that microRNA (miR)‑17‑5p targets the 3'untranslated region (3'UTR) of E2F1. The aim of the present study was to characterize the protective effect of miR‑17‑5p/E2F1 on human umbilical vein endothelial cells (HUVECs) under high glucose (HG) conditions, to confirm the regulatory effect of miR‑17‑5p on E2F1/AMP‑activated protein kinase α2 (AMPKα2)‑mediated apoptosis and E2F1/mammalian target of rapamycin complex 1 (mTORC1)‑mediated autophagy. Bifluorescein experiments were performed to characterize the interaction between miR‑17‑5p and E2F1. The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence, and reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect cell viability, apoptosis, autophagy, and relative mRNA and protein expression, respectively. The results showed that HG induced the downregulation of miR‑17‑5p and upregulation of E2F1 during HUVEC injury. The downregulation of E2F1 inhibited HG‑induced HUVEC dysfunction by suppressing mTORC1‑mediated inhibition of autophagy and AMPKα2‑mediated promotion of apoptosis. The results suggested that inhibiting the expression of E2F1 protected against HG‑induced HUVEC injury via the activation of autophagy. The overexpression of miR‑17‑5p inhibited E2F1‑mediated HUVEC injury under HG conditions, which was reversed following transfection with an E2F1‑overexpression vector. The bifluorescein experiments showed that miR‑17‑5p targeted the 3'UTR of E2F1. Taken together, the results suggested that the expression of miR‑17‑5p inhibited HG‑induced endothelial cell injury by targeting E2F1.

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

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Adipose‐derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis

“…miR‐24, miR‐106a and miR‐130a‐3p alleviate hyperglycemia‐induced podoplanin cellular inflammation and apoptosis in diabetic nephropathy 116–118 . miR‐17‐5p and miR‐24 protect against hyperglycemia‐induced endothelial cell damage and enhance autophagy in DM‐associated endothelial dysfunction 119,120 . As these miRNAs are significantly downregulated in obesity, they could indicate imminent complications of T2DM.…”

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1

“…E2F1 is involved in cell cycle regulation, apoptosis signal transduction, cell growth, metastasis, autophagy, and other processes ( Yuan et al, 2018 ). The study demonstrated the specific biological function of E2F1 in the progression and related complications of DM.…”