摘 要：肝癌是全球癌症相关死亡的第三大原因，生存率低且容易复发。为探究circHIPK3在肝癌中的调控机制，本研究通过实时荧光定量PCR方法分析HIPK3及其环状RNA circHIPK3的表达水平，结果显示，两者在肝癌细胞中显著上调。进一步通过双荧光素酶报告基因试验验证，circHIPK3直接与miR-599结合，且miR-599可靶向结合CD276的3'UTR区域。此外，构建si-circHIPK3稳定转染的肝癌细胞株并转染miR-599进行功能研究，结果表明，circHIPK3能够通过“海绵”吸附miR-599，从而解除其对CD276的抑制作用，促进CD276表达，进而增强肝癌细胞的增殖和迁移能力。本研究聚焦于circHIPK3/miR-599/CD276调控轴在肝癌中的调控作用机制，为阐明其恶性生物学行为提供了新的分子依据，提示其可能成为潜在的治疗靶点。

关键词：肝癌；‌环状同源域相互作用蛋白激酶；微小核糖核酸-599；分化簇276；治疗靶点
中图分类号：Q254；R735.7        文献标志码：A                DOI：10.3969/j.issn.1007-7146.2025.05.004

Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide, characterized by poor prognosis and a high recurrence rate. To investigate the regulatory mechanism of circHIPK3 in HCC, we analyzed the expression levels of HIPK3 and its circular RNA isoform, circHIPK3, using quantitative real-time PCR (qRT-PCR), and found both to be significantly upregulated in HCC cells. Dual-luciferase reporter assays confirmed that circHIPK3 directly binds to miR-599, and that miR-599 targets the 3'untranslated region (UTR) of CD276. Furthermore, we established a stable HCC cell line with circHIPK3 knockdown (si-circHIPK3) and transfected miR-599 mimics to assess functional consequences. The results demonstrated that circHIPK3 can act as a competing endogenous RNA (ceRNA) to sponge miR-599, thereby alleviating its inhibitory effect on CD276 and upregulating CD276 expression, and enhancing the proliferation and migration ability of HCC cells. Collectively, our findings elucidate the circHIPK3/miR-599/CD276 regulatory axis in HCC progression, providing novel molecular insights into the malignant behavior of HCC cells and highlighting a potential therapeutic target.
Key words: hepatocellular carcinoma; circHIPK3; miR-599; CD276; therapeutic target
（Acta Laser Biology Sinica, 2025, 34(5): 409-416）