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

Shao, Jun; Cai, Jiping; Yao, Yong; Zhu, Hui

doi:10.21037/atm-21-5562

Cited by 3 publications

(1 citation statement)

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“…These results suggested SKP1 is a direct downstream molecule of PTPN12, and that EGFR is a potential downstream factor of the PTPN12-SKP1 complex, although further investigation is required to determine the details. Additionally, as inflammation has been considered as a central role player in DR, and in our previous work, the antagonistic mechanism of miR-1243 against RELB/ circ_0008590 in NF-κB non-classic pathway was proved to repress the NV progression of DR (28); in this work, we tried to investigate the relationship between circ_0007411 and classic inflammation signaling pathways, however, the overexpression and knockdown of circ_0007411 could not affect the factors in NF-κB, TLR and Jak/Stat pathways. As circ_0007411 and miR-548m are not conserved in mice, in this work, the function of PTPN12 was investigated by establishing an STZ-induced model of DR in C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 86%

Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway

Hu¹,

Tian²,

Lu³

et al. 2022

Ann Transl Med

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Background: To investigate the mechanism of transthyretin (TTR) induced high expression of circ_0007411 and its parent gene, protein tyrosine phosphatase nonreceptor type 12 (PTPN12) in human retinal microvascular endothelial cells (hRECs) cultivated under high glucose condition. Methods:The levels of PTPN12, circ_0007411, miR-548m, S-phase kinase associated protein 1 (SKP1) and epidermal growth factor receptor (EGFR) were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The direct interaction between circ_0007411/PTPN12 and miR-548m was investigated via Dual-luciferase reporter assay. The physiological characterization of hRECs was investigated through Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labelling, Transwell, flow cytometry (FCM), wound healing, and tube formation assays. Co-immunoprecipitation (Co-IP) was used to detect the interaction between PTPN12 and SKP1. The function of PTPN12 against diabetic retinopathy (DR) was studied in streptozotocin (STZ) induced DR C57BL/6 mice.Results: The levels of circ_0007411 was increased in hRECs in hyperglycemia with the induction of TTR.The overexpressed circ_0007411 could significantly enhance the level of PTPN12 and repress that of miR-548m, and it could enhance apoptosis and prohibit the proliferation, migration, and tube formation of hRECs. miR-548m mimics enhanced the proliferation, migration, and tube formation of hRECs by reducing the expression level of PTPN12 and promoting that of EGFR, whereas circ_0007411 rescued it. The direct binding of PTPN12 and SKP1 was confirmed by Co-IP. Additionally, the anti-neovascularization function of PTPN12 was confirmed in a STZ-induced mouse model of DR. Conclusions:In hyperglycemia, the TTR-induced increase in circ_0007411 could repress retinal neovascularization via the miR-548m/PTPN12/SKP1/EGFR pathway.

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Section: Discussionmentioning

confidence: 86%