CircRAB23 functions as miR-532-3p sponge to promote the malignant proliferation and metastasis of intrahepatic cholangiocarcinoma through HMGA2-EMT axis

The incidence and mortality rate of intrahepatic cholangiocarcinoma (ICC) have increased dramatically in recent years. ICC develops quickly and readily metastasizes, but good clinical biomarkers and treatment targets are lacking, resulting in a dismal prognosis. Previously, we reported that the circular RNA hsa_circ_0004119, which is generated by RAB23, is significantly overexpressed in ICC tissues. In this study, we found that the circularization of the second to sixth exons of the parent gene is the primary mechanism of circRAB23 cyclization. circRAB23 expression was upregulated in both ICC tissues and cell lines and was positively correlated with tumour size, the presence of pathological satellite lesions, vascular invasion, poor differentiation, and lymph node metastasis. Moreover, patients with higher expression of circRAB23 had shorter overall survival (OS) and disease-free survival (DFS). circRAB23 overexpression promoted the malignant proliferation, invasion and migration of ICC cells. Interference with circRAB23 expression had the opposite effect. Mechanistic and functional studies in both in vivo and in vitro settings revealed that highly expressed circRAB23 acts as a sponge for miR-532-3p, deregulating the inhibitory effect of miR-532-3p on HMGA2 and thereby affecting the epithelial mesenchymal transition (EMT)-related signalling pathway and promoting tumour cell invasion and metastasis. In conclusion, circRAB23 promotes malignant proliferation and metastasis in ICC via the miR-532-3p/HMGA2/EMT axis, making it a promising diagnostic and therapeutic target for ICC.