Hsa_circ_001726 axis contributes to metastasis of hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. CircRNAs participate in the development of HCC. This work aims to search a key circRNA that plays an important role in HCC. The differentially expressed genes circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. We found that 11 circRNAs were up-regulated in tumor tissues of HCC patients with or without metastasis. Among them, hsa_circ_001726 was highly expressed in tumor tissues of HCC patients with or without metastasis, and associated with tumor size, TNM stages and poor prognosis of HCC patients. Hsa_circ_001726 expression was positively correlated with N-cadherin expression, and negatively correlated with E-cadherin expression, indicating that it was closely associated with epithelial mesenchymal transition (EMT) of HCC cells. Moreover, hsa_circ_001726 expression was increased in HCC cells. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including migration, invasion and EMT. In vivo, Xenograft mouse models and orthotopic transplantation tumor mouse models were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. Hsa_circ_001726 deficiency reduced tumor growth and metastasis of HCC. In conclusion, this work demonstrated that hsa_circ_001726 activated Notch signaling pathway via miR-671-5p/PRMT9 axis, thereby accelerating malignant progression and metastasis of HCC. Therefore, hsa_circ_001726 may be a biomarker for diagnosis and prognosis of HCC.