Background and Aims Hepatocellular carcinoma (HCC) is among the most common malignant tumors globally. Circular RNAs (circRNAs), as a type of noncoding RNAs, reportedly participate in various tumor biological processes. However, the role of circHDAC1_004 in HCC remains unclear. Thus, we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect circHDAC1_004 expression (circ_0005339) in HCC. Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004. In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC. Herein, qRT-PCR, RNA immunoprecipitation, western blotting, and a luciferase reporter assay were used to explore the relationships among circHDAC1_004, miR-361-3p, and NACC1. Results circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival. circHDAC1_004 promoted HCC cell proliferation, stemness, migration, and invasion. In addition, circHDAC1_004 upregulated human umbilical vein endothelial cells (HUVECs) and promoted angiogenesis through exosomes. circHDAC1_004 promoted NACC1 expression and stimulated the epithelial-mesenchymal transition pathway by sponging miR-361-3p. Conclusions We found that circHDAC1_004 overexpression enhanced the proliferation, stemness, and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes. Our findings may help develop a possible therapeutic strategy for HCC.

中文翻译：

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外泌体转运的 circHDAC1_004 通过 miR-361-3p/NACC1 轴促进肝细胞癌的增殖、迁移和血管生成。

背景和目的肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。据报道，环状RNA（circRNA）作为一种非编码RNA参与多种肿瘤生物学过程。然而，circHDAC1_004 在 HCC 中的作用仍不清楚。因此，我们旨在探讨circHDAC1_004在HCC发生和进展中的作用和潜在机制。方法采用实时定量聚合酶链式反应（qRT-PCR）检测HCC中circHDAC1_004（circ_0005339）的表达。采用Sanger测序和琼脂糖凝胶电泳确定circHDAC1_004的结构。采用体外和体内实验确定circHDAC1_004在HCC中的生物学功能。在此，使用qRT-PCR、RNA免疫沉淀、蛋白质印迹和荧光素酶报告基因测定来探索circHDAC1_004、miR-361-3p和NACC1之间的关系。结果 circHDAC1_004 在 HCC 中表达上调，并且与较差的总体生存率显着相关。circHDAC1_004 促进 HCC 细胞增殖、干性、迁移和侵袭。此外，circHDAC1_004上调人脐静脉内皮细胞（HUVEC）并通过外泌体促进血管生成。circHDAC1_004 通过海绵 miR-361-3p 促进 NACC1 表达并刺激上皮间质转化途径。结论我们发现circHDAC1_004过表达通过miR-361-3p/NACC1轴增强HCC的增殖、干性和转移，并通过外泌体促进HCC血管生成。我们的研究结果可能有助于制定一种可能的 HCC 治疗策略。