Xu Bin, Jia Wenbo, Feng Yanzhi, Wang Jinyi, Wang Jing, Zhu Deming, Xu Chao, Liang Litao, Ding Wenzhou, Zhou Yongping, Kong Lianbao
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, China.
J Clin Transl Hepatol. 2023 Oct 28;11(5):1079-1093. doi: 10.14218/JCTH.2022.00097. Epub 2023 Mar 22.
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.
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. and 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.
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.
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.
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。环状RNA（circRNAs）作为一类非编码RNA，据报道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发生发展及进展中的作用和潜在机制。
采用定量实时聚合酶链反应（qRT-PCR）检测HCC中circHDAC1_004（circ_0005339）的表达。使用桑格测序和琼脂糖凝胶电泳确定circHDAC1_004的结构。 实验用于确定circHDAC1_004在HCC中的生物学功能。在此，采用qRT-PCR、RNA免疫沉淀、蛋白质印迹和荧光素酶报告基因检测来探究circHDAC1_004、miR-361-3p和NACC1之间的关系。
circHDAC1_004在HCC中上调，且与总体生存率差显著相关。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（HUVECs）并通过外泌体促进血管生成。circHDAC1_004通过海绵吸附miR-361-3p促进NACC1表达并激活上皮-间质转化途径。
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开发一种针对HCC的潜在治疗策略。
