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

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/AKK3 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.