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. 2025 Mar 3;72(3):295-306.
doi: 10.1507/endocrj.EJ24-0440. Epub 2025 Jan 7.

LncRNA A1BG-AS1 regulates the progress of diabetic foot ulcers via sponging miR-214-3p

Fangfang Wu  1 , Lixia Wang  2 , Hongju Zuo  1 , Hanbing Tian  1
Affiliations

LncRNA A1BG-AS1 regulates the progress of diabetic foot ulcers via sponging miR-214-3p

Fangfang Wu et al. Endocr J. .

Abstract

Nerve aberrations and vascular lesions in the distal lower limbs are the etiological factors for diabetic foot ulcers (DFUs). This study aimed to understand the regulatory mechanism of angiogenesis in patients with DFU by examining lncRNA, as well as to explore effective targets for diagnosing and treating DFU. The serum levels of A1BG-AS1 and miR-214-3p and the predictive power of A1BG-AS1 for DFU were determined by quantitative PCR and ROC analysis. The correlation of A1BG-AS1 with clinical characteristics was examined using chi-square tests. The risk factors for DFU in patients with type 2 diabetes mellitus (T2DM) were identified using the logistic regression model. Furthermore, the binding sites of A1BG-AS1 and miR-214-3p were determined. Next, A1BG-AS1 interference plasmid and miR-214-3p inhibitor were co-transfected into high glucose-induced cells to investigate their effects on the expression of angiogenesis-related genes and cell proliferation. The A1BG-AS1 levels were upregulated, whereas the miR-214-3p levels were downregulated in patients with DFU. The upregulation of A1BG-AS1 was significantly associated with both blood glucose levels and ulcer grades. A1BG-AS1 served as a crucial biomarker for diagnosing DFU and evaluating the risk of DFU occurrence in patients with T2DM. Co-transfection experiments revealed that the inhibition of miR-214-3p effectively recovered the suppressive effects of A1BG-AS1 on angiogenesis-related gene expression, endothelial cell differentiation, and proliferation. The sponging effect of A1BG-AS1 on miR-214-3p impaired angiogenesis in patients with DFU. Thus, A1BG-AS1 is a potential therapeutic target for DFU.

Keywords: Angiogenesis; Diabetic foot ulcers; Diagnostic; LncRNA; miRNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1. The expression level in the serum and the diagnostic significance of lncRNA A1BG-AS1 in DFU patients. A, the expression levels of A1BG-AS1. B, ROC curve analysis. ***, p < 0.001.
Fig. 2
Fig. 2. The relationship between lncRNA A1BG-AS1 and miR-214-3p. A, the binding sites. B, miR-214-3p targeted binding to A1BG-AS1-WT. C, miR-214-3p targeted binding to A1BG-AS1-MUT. D, the levels of miR-214-3p in controls and patients with T2DM and DFU. E, the correlation between A1BG-AS1 and miR-214-3p in the DFU group. **, p < 0.01; ***, p < 0.001.
Fig. 3
Fig. 3. The effects of co-transfection si-A1BG-AS1 and miR-214-3p inhibitor on the expression of related genes, as well as HDFa cell proliferation. A, the levels of A1BG-AS1. B, the levels of miR-214-3p. C, the changes in cell proliferation. D, the levels of mafG. E, the levels of SDF-1α. F, the levels of VEGF. ***, p < 0.001 versus control groups. &&, p < 0.01; &&&, p < 0.001 versus HG groups. $, p < 0.05; $$, p < 0.01; $$$, p < 0.001 versus HG + si-A1BG-AS1 groups.
Graphical Abstract
Graphical Abstract
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