Circulating miR-378a-3p Screens End-Stage Renal Disease Patients, Predicts the Occurrence of MACEs, and Regulates Vascular Calcification via Targeting SULF1.

End-stage renal disease (ESRD) threatens human lives due to the high incidence rate of complications. Vascular calcification is a severe complication of ESRD inducing major adverse cardiovascular events (MACEs). This study enrolled 205 patients diagnosed with chronic kidney disease (CKD), including 95 patients diagnosed at end stages. The clinical significance of miR-378a-3p was assessed from the perspectives of early screening, risk prediction, and MACE prediction. The regulation of vascular calcification by miR-378a-3p was estimated through inflammation, osteogenic differentiation, Ca2+ concentration, and cell proliferation in human vascular smooth muscle cells (hVSMCs). Significant downregulation of miR-378a-3p was observed in ESRD patients, which discriminated ESRD patients from early-stage CKD patients and predicted the risk of ESRD. Lower serum miR-378a-3p levels were observed in ESRD patients developing vascular calcification and were identified as a risk factor for the occurrence of MACEs. Overexpression of miR-378a-3p could alleviate calcified culture medium-induced inflammation, osteogenic differentiation, increasing Ca2+, and decreasing cell proliferation of hVSMCs. SULF1 was negatively regulated by miR-378a-3p. The overexpression of SULF1 reversed the protective effect of miR-378a-3p on vascular calcification. miR-378a-3p acted as a biomarker for screening ESRD and predicting adverse outcomes of patients. miR-378a-3p regulated vascular calcification through targeting SULF1.