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Background <p>Diabetic retinopathy (DR), a leading blinding microvascular complication of type 2 diabetes mellitus (T2DM), is projected to affect 161&#xa0;million people globally by 2045.</p> Methods <p>This study enrolled 261 participants (127 T2DM controls and 134 T2DM with DR). Serum miR-501-5p levels were analyzed by qRT-PCR. Human Retinal Microvascular Endothelial Cells (HRMECs) under high-glucose conditions were transfected to modulate miR-501-5p expression or overexpress <i>NR2F2</i>. The miR-501-5p–<i>NR2F2</i> interaction was verified by dual-luciferase assay. Cell proliferation, VEGF, ROS, and endoplasmic reticulum stress markers (GRP78, CHOP) were assessed.</p> Results <p>miR-501-5p was identified as an independent protective factor for DR, showing significant downregulation in T2DM patients and high diagnostic accuracy (AUC = 0.907). In high-glucose conditions, miR-501-5p overexpression reduced VEGF, ROS, and ER stress markers and improved cell proliferation. <i>NR2F2</i> was confirmed as a direct target of miR-501-5p, and its overexpression reversed the protective effects of miR-501-5p.</p> Conclusion <p>These findings suggest that miR-501-5p is strongly associated with DR and may serve as a potential biomarker and protective agent, possibly through targeting <i>NR2F2</i> to ameliorate high glucose-induced retinal microvascular damage.</p>

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miR-501-5p mediates the progression of type 2 diabetic retinopathy by targeting NR2F2

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Jinling Liu,
  • Jiao Liu,
  • Haihui Li,
  • Linling Kong,
  • Yaqin Hu,
  • Lu Zhou

摘要

Background

Diabetic retinopathy (DR), a leading blinding microvascular complication of type 2 diabetes mellitus (T2DM), is projected to affect 161 million people globally by 2045.

Methods

This study enrolled 261 participants (127 T2DM controls and 134 T2DM with DR). Serum miR-501-5p levels were analyzed by qRT-PCR. Human Retinal Microvascular Endothelial Cells (HRMECs) under high-glucose conditions were transfected to modulate miR-501-5p expression or overexpress NR2F2. The miR-501-5p–NR2F2 interaction was verified by dual-luciferase assay. Cell proliferation, VEGF, ROS, and endoplasmic reticulum stress markers (GRP78, CHOP) were assessed.

Results

miR-501-5p was identified as an independent protective factor for DR, showing significant downregulation in T2DM patients and high diagnostic accuracy (AUC = 0.907). In high-glucose conditions, miR-501-5p overexpression reduced VEGF, ROS, and ER stress markers and improved cell proliferation. NR2F2 was confirmed as a direct target of miR-501-5p, and its overexpression reversed the protective effects of miR-501-5p.

Conclusion

These findings suggest that miR-501-5p is strongly associated with DR and may serve as a potential biomarker and protective agent, possibly through targeting NR2F2 to ameliorate high glucose-induced retinal microvascular damage.