Evidence map›Paper›PMID 42471691›Full record

ArticleJournal of translational medicine2026

circKIAA1462 impaires autophagy and promotes pyroptosis in retinal pigment epithelium via the miR-183-5p/HMGB1 axis in diabetic retinopathy.

Lufei Wang, Jia'nan Xie, Longfei Yang, Jinsong Zhao, Xin Liu

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Lufei WangEye Center, The Second Hospital of Jilin University, Changchun, 130021, China.
Jia'nan XieEye Center, The Second Hospital of Jilin University, Changchun, 130021, China.
Longfei YangJilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, 130021, China.
Jinsong ZhaoEye Center, The Second Hospital of Jilin University, Changchun, 130021, China.
Xin LiuEye Center, The Second Hospital of Jilin University, Changchun, 130021, China. dr_liuxin@jlu.edu.cn.ORCID http://orcid.org/0000-0001-9743-3934

Funding

National Natural Science Foundation of China 82000920the Bethune plan of Jilin University 2025B30
6 · The paper itself

Abstract

backgroundDiabetic retinopathy (DR) is one of the most prevalent complications of diabetes which could lead to vision impairment. Dysfunction of the retinal pigment epithelium (RPE) is an early pathogenic event, where various mechanisms may contribute to the disease progression. circular RNAs (circRNAs) have been reported to be important regulators in diabetic complications, acting as miRNA sponge, participating in the regulation of gene transcription or coding short peptides.

methodsCircular RNA microarray and RNA-seq were used to identify differentially expressed circRNAs in ARPE-19 cells in normal and high glucose treatments. The expression of cKIAA1462, miR-183-5p, and high mobility group box 1 (HMGB1) were determined using quantitative real-time polymerase chain reaction and Western blot. In vitro experiments, such as flow cytometry, Western blot, and Electron microscope (TEM) were conducted. The binding interaction was confirmed using dual-luciferase reporter and overexpression/inhibition experiments. cKIAA1462 was knocked down via intravitreal lentiviral injection in diabetic mice, followed by expression level detection, functional analysis and histological assessments.

resultscKIAA1462 was significantly upregulated under high glucose conditions both in vitro and in vivo (in retinas of diabetic mice). It acted as a molecular sponge for miR-183-5p, increasing the expression of HMGB1. Elevated HMGB1 concurrently impaired autophagic flux (increased p62, decreased autophagosomes) and activated the NLRP3 inflammasome (upregulated NLRP3, ASC, caspase-1), promoting pyroptosis. Silencing cKIAA1462 in vivo restored autophagy, suppressed pyroptosis, improved retinal structure, and enhanced electroretinogram responses in diabetic mice.

conclusionThe cKIAA1462/miR-183-5p/HMGB1 axis plays a critical role in diabetic RPE injury by dual regulation of autophagy and pyroptosis. Targeting this pathway may offer a novel therapeutic strategy for early diabetic retinopathy.

Indexed as

AutophagyDiabetic RetinopathyHMGB1 ProteinMicroRNAsPyroptosisRetinal Pigment EpitheliumRNA, CircularAnimalsBase SequenceCell LineDiabetes Mellitus, ExperimentalGlucoseHumansMaleMiceMice, Inbred C57BLGlucoseHMGB1 ProteinMicroRNAsMIRN183 microRNA, humanMirn183 microRNA, mouseRNA, CircularAutophagycircKIAA1462Diabetic retinopathyHMGB1microRNA-183-5pPyroptosis

Identifiers

PMID42471691
PMCPMC13673722

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.