The role of hsa_circ_0004662 in non-alcoholic fatty liver disease: diagnostic potential and mechanistic insights

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is a progressive disease. The diagnostic performance of current non-invasive biomarkers for NAFLD remains suboptimal. Circular RNAs (circRNAs) have emerged as potential biomarkers and therapeutic targets due to their involvement in disease progression. This study investigated the diagnostic potential and underlying mechanisms of hsa_circ_0004662 in NAFLD. Methods The study combined bioinformatics and experimental approaches. Analysis of the GSE134146 dataset revealed differentially expressed circRNAs, leading to RT-qPCR verification of hsa_circ_0004662 in clinical cohorts. Cellular models were utilized to assess triglyceride (TG) content in HepG2 cells and fibrosis markers in LX-2 cells; potential miRNA interactions were examined through integrated prediction and validation. Results Screening of the GSE134146 dataset revealed that hsa_circ_0004662 was the most markedly upregulated circRNA. This finding was confirmed in our independent clinical cohort, comprising 156 NAFLD patients and 105 healthy controls. Compared with healthy controls, the expression of hsa_circ_0004662 was gradually upregulated in plasma samples of patients with non-alcoholic steatohepatitis (NASH) and NASH-associated liver fibrosis (NASH-AF). hsa_circ_0004662 promoted lipid accumulation in HepG2 cells and fibrosis in LX-2 cells. Mechanistically, hsa_circ_0004662 likely interacts with miR-532-3p to promote NAFLD. Conclusions Hsa_circ_0004662 holds potential as a non-invasive diagnostic biomarker and therapeutic target for NAFLD. Further validation and mechanistic studies are warranted to elucidate its role in disease progression.