miR-151a-5p predicts severity of diabetic retinopathy and protects from retinal cell injury by inactivating MAPK signaling via DKK3

Abstract

Diabetes mellitus (DM) is always accompanied by various complications, where diabetic retinopathy was a serious microvascular complications threatening the visual function of patients. This study evaluated the significance of miR-151a-5p and its effect on DR progression aiming to explore a novel biomarker for disease screening and monitoring. Study enrolled 137 patients with DM and 103 diabetes patients with DR. Serum miR-151a-5p was compared with PCR, and its clinical significance was evaluated from the perspectives of diagnosis and severity prediction. High-glucose-treated human retinal cell model was established, the effect of miR-151a-5p on high-glucose-induced cell injury was assessed based on cell growth, inflammation, oxidative stress, and endoplasmic reticulum stress. In mechanism, the downstream targets of miR-151a-5p were predicted, based on the function enrichment, the involvement of DKK3 and the MAPK signaling was estimated. Increasing miR-151a-5p was identified as a risk factor for DR in DM patients diagnosing DR patients and was positively correlated with disease severity predicting severe development of DR. Silencing miR-151a-5p alleviated high-glucose-induced reducing proliferation, activated inflammation, oxidative stress, and endoplasmic reticulum stress in human retinal cells. Negative regulation of DKK3 by miR-151a-5p was observed, and the knockdown of DKK3 could reversed the protective effect of miR-151a-5p. High-glucose activate the MAPK signaling, which was suppressed by the miR-151a-5p/DKK3 axis, and MAPK signaling was demonstrated to mediate the functional role of the miR-151a-5p/DKK3 axis. miR-151a-5p can be considered as a biomarker for the onset and progression of DR. miR-151a-5p potentially modulates the progression of DR through regulating inflammation, oxidative stress, and endoplasmic reticulum stress via the MAPK signaling.

Keywords: Diagnostic biomarker; MAPK signaling; Retinal cell injury; Severity prediction; Target gene.