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）