CircHIPK3 relieves vascular calcification via mediating SIRT1/PGC-1α/MFN2 pathway by interacting with FUS

• Published in: BMC cardiovascular disorders Vol. 23; no. 1; p. 583
• Main Authors: Feng, Siyi, Qi, Youfei, Xiao, Zhanxiang, Chen, Hao, Liu, Sahua, Luo, Haimei, Wu, Hongfei, Zhang, Wenbo
• Format: Journal Article
• Language: English
• Published: England BioMed Central 27.11.2023; BMC
• Subjects: Alkaline phosphatase; Antibodies; Arteriosclerosis; Biotechnology; Calcification; Calcification (ectopic); Calcium - metabolism; Cell culture; CircHIPK3; Circular RNA; FUS; FUS protein; Gene expression; GTP Phosphohydrolases - metabolism; Hospitals; Humans; Immunoprecipitation; Medical research; Mitochondrial Proteins - metabolism; mRNA; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Peroxisome proliferator-activated receptors; Polymerase chain reaction; Proteins; Reagents; RNA, Circular - genetics; RNA-Binding Protein FUS; Sarcoma; Signal transduction; SIRT1 protein; SIRT1/PGC-1α signaling; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Smooth muscle; Vascular Calcification - genetics; Vascular Calcification - metabolism; β-Glycerophosphoric acid; United States > US; China; Calcification; SIRT1/PGC-1α signaling; CircHIPK3; FUS
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-023-03602-3

Circular RNAs (circRNAs) have been reported to regulate the biological processes of human diseases. CircHIPK3 has been implicated in vascular calcification, but the downstream regulatory mechanisms remain unclear. Our study aimed to understand the regulatory function of circHIPK3 in vascular calcification. CircHIPK3 expression in atherosclerosis (AS) serum samples and vascular smooth muscle cells (VSMCs) calcification model was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The binding relationships between fused in sarcoma (FUS) and circHIPK3 or sirtuin 1 (SIRT1) were verified by RNA immunoprecipitation (RIP) assay and RNA pull-down assays. Alkaline phosphatase (ALP) activity and alizarin red staining assays were performed to evaluate the biological effect of β-glycerophosphate (β-GP) and circHIPK3 on calcium deposition. qRT-PCR and western blot assays were used to examine the effect of β-GP, circHIPK3, SIRT1, mitofusin 2 (MFN2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) on VSMCs calcification and the expression of calcification-related proteins. In AS serum samples and VSMCs calcification model, the expression of circHIPK3 was significantly reduced. CircHIPK3 overexpression inhibited ALP activity and calcium deposition in β-GP-induced VSMCs. Moreover, circHIPK3 could recruit FUS to further stabilize SIRT1 mRNA. CircHIPK3 promoted MFN2 expression to alleviate VSMCs calcification via activating SIRT1/PGC-1α signaling. The positive regulation of circHIPK3/FUS/SIRT1/PGC-1α/MFN2 signaling pathway contributed to the alleviate VSMCs calcification, revealing a novel regulatory axis for vascular calcification.