Zhang Xiaobo, Li Suxin, Li Luhao, Li Dingyang, Zhao Huashan, Gao Xiaole, Dang Xiaowei
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Key Laboratory of Precision Diagnosis and Treatment in General Surgical (Hepatobiliary and Pancreatic) Diseases of Health Commission of Henan Province, Zhengzhou, China.
J Cancer. 2025 Mar 31;16(7):2275-2288. doi: 10.7150/jca.103661. eCollection 2025.
: This study aimed to investigate the impact of circ_0046599 on hepatocellular carcinoma (HCC). Analysis of the GEO dataset identified circ_0046599 as significantly upregulated in HCC, and its impact on cell proliferation, apoptosis, migration, and invasion was assessed. Bioinformatics and dual-luciferase assays identified miR-1322 as a target of circ_0046599, which in turn regulates NT5DC2 expression. In vitro and in vivo experiments confirmed the ceRNA mechanism of circ_0046599 in HCC. circ_0046599 was significantly upregulated in HCC, and predicts a worse survival in HCC patients. Increased expression of circ_0046599 promoted HCC cell proliferation, migration, invasion, and inhibited apoptosis. circ_0046599 bound to miR-1322, which exerted a tumor-suppressive effect in HCC cells. miR-1322 targeted NT5DC2, and circ_0046599 regulated the expression of NT5DC2 by competitively binding to miR-1322. Modulation of NT5DC2 expression affected the oncogenic role of circ_0046599. In experiments, inhibition of circ_0046599 suppressed the growth of xenograft tumors by upregulating miR-1322 expression and suppressing NT5DC2. : circ_0046599 promoted the progression of HCC by competitively binding to miR-1322 and regulating the expression of NT5DC2.
本研究旨在探讨circ_0046599对肝细胞癌（HCC）的影响。对GEO数据集的分析表明，circ_0046599在HCC中显著上调，并评估了其对细胞增殖、凋亡、迁移和侵袭的影响。生物信息学和双荧光素酶测定确定miR-1322是circ_0046599的靶标，miR-1322进而调节NT5DC2的表达。体外和体内实验证实了circ_0046599在HCC中的ceRNA机制。circ_0046599在HCC中显著上调，并预示HCC患者的生存期较差。circ_0046599表达增加促进了HCC细胞的增殖、迁移、侵袭，并抑制了细胞凋亡。circ_0046599与miR-1322结合，miR-1322在HCC细胞中发挥肿瘤抑制作用。miR-1322靶向NT5DC2，circ_0046599通过竞争性结合miR-1322调节NT5DC2的表达。NT5DC2表达的调节影响了circ_0046599的致癌作用。在实验中，抑制circ_0046599通过上调miR-1322表达和抑制NT5DC2来抑制异种移植肿瘤的生长。circ_0046599通过竞争性结合miR-1322并调节NT5DC2的表达促进了HCC的进展。
