Hyperglycemia-induced increasing of RELB/circ_0008590 in NF-κB pathway is repressed by miR-1243 in human retinal microvascular endothelial cells

Jun Shao; Jiping Cai; Yong Yao; Hui Zhu

doi:10.21037/atm-21-5562

Hyperglycemia-induced increasing of RELB/circ_0008590 in NF-κB pathway is repressed by miR-1243 in human retinal microvascular endothelial cells

Ann Transl Med. 2021 Nov;9(21):1624. doi: 10.21037/atm-21-5562.

Authors

Jun Shao^#¹, Jiping Cai^#¹, Yong Yao¹, Hui Zhu²

Affiliations

¹ Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
² State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: To investigate the abnormal expression of circ_0008590 and its parent gene, reticuloendotheliosis viral oncogene related B (RELB) in human retinal microvascular endothelial cells (hRECs) in hyperglycemia and the potential mechanism.

Methods: The levels of RELB, circ_0008590, and miR-1243 in hRECs or clinical samples were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Dual-luciferase reporter assay was used to test the interaction between RELB/circ_0008590 and miR-1243. Cell Counting Kit-8 (CCK-8), Transwell, flow cytometry (FCM), wound healing, and tube formation assays were used for the physiological investigation. The interaction between human RELB and circ_0008590 was studied in streptozotocin (STZ) induced diabetic retinopathy (DR) C57BL/6 mice.

Results: The levels of circ_0008590 and RELB were increased in hRECs in hyperglycemia; during the progression of DR, the levels of circ_0008590 and RELB messenger RNA (mRNA) in aqueous humor were first decreased and then increased, whereas miR-1243 showed an opposite trend. Both RELB 3'-untranslated region (UTR) and circ_0008590 shared a similar binding site for miR-1243. Further, miR-1243 mimic suppressed the proliferation and migration of hRECs, promoting the apoptosis ratio, which could be rescued by the overexpression of circ_0008590. In STZ-induced DR mice, miR-1243 agomir rescued the effects of the overexpression of human RELB.

Conclusions: In hyperglycemia, high expression of RELB/circ_0008590 could be suppressed by miR-1243, and the nuclear factor-κB (NF-κB) pathway is subsequently affected.

Keywords: Diabetic retinopathy (DR); circ_0008590; hyperglycemia; miR-1243; reticuloendotheliosis viral oncogene related B (RELB).