Clinical significance and functional role of miR-3663-3p in vascular calcification associated with chronic kidney disease

Vascular calcification (VC) is a common and serious complication of chronic kidney disease (CKD). MicroRNAs (miRNAs) play important regulatory roles in VC. Identifying abnormally expressed miRNAs may offer novel strategies for clinical intervention. This study aimed to investigate the clinical value of miR-3663-3p in CKD and VC, as well as its regulatory role in VC. This study included 102 healthy controls and 118 patients with CKD. RT-qPCR was used to detect the expression of miR-3663-3p. Receiver operating characteristic (ROC) and logistic regression evaluated the diagnostic value and risk prediction of miR-3663-3p in CKD-related VC. Calcium deposition model of human aortic smooth muscle cells (HASMCs) was induced by high inorganic phosphate (Pi). The calcium content, mRNA levels of HASMC markers (α-SMA, SM22α), and levels of osteogenic markers (Runx2, BMP-2, ALP) were evaluated. A dual-luciferase assay verified that miR-3663-3p directly targets cAMP responsive element modulator (CREM). Compared with healthy controls, the expression of miR-3663-3p is upregulated in CKD patients, especially those with VC. MiR-3663-3p has high diagnostic value for CKD and its VC. In the HASMC calcification model, the level of miR-3663-3p, the amount of calcium, and the osteogenic differentiation markers (Runx2, BMP-2, ALP) all increase, while the transcriptional levels of HASMC markers (α-SMA, SM22α) decrease. Inhibiting miR-3663-3p can effectively reverse the osteogenic differentiation of Pi-induced HASMCs, while overexpressing miR-3663-3p promotes this process. CREM is a downstream target of miR-3663-3p. Knockdown of CREM can reverse the anti-calcification effect induced by miR-3663-3p inhibition. MiR-3663-3p demonstrates diagnostic potential for CKD and its complication VC, likely by targeting CREM to promote osteogenic differentiation of HASMCs, thereby advancing the VC process.