环形RNA（circRNAs）是非编码RNA。越来越多的证据表明，circRNAs在人类生物过程中，特别是在肿瘤发生和发展中发挥着关键作用。然而，circRNAs在肝细胞癌（HCC）中的作用机制仍不清楚。利用生物信息学工具和RT-qPCR识别circDHPR（一种来自二氢叶酸还原酶（DHPR）基因组的circRNA）在HCC和癌旁组织中的作用。采用Kaplan-Meier分析和Cox比例风险模型分析circDHPR表达与患者预后之间的相关性。利用慢病毒载体建立稳定的circDHPR过表达细胞。体内外研究表明，circDHPR会影响肿瘤的增殖和转移。机理试验包括：西方印迹、免疫组织化学、双荧光素酶报告基因实验、原位杂交和RNA免疫共沉淀等，证明circDHPR的分子机制。circDHPR在HCC中表达下降，低circDHPR表达与低总生存率和无疾病生存率相关。circDHPR的过表达抑制了体内外的肿瘤生长和转移。进一步系统的研究表明，circDHPR可以结合miR-3194-5p（RASGEF1B上游调节因子），这种内源性竞争抑制了miR-3194-5p的沉默效应。我们证实，通过吸附miR-3194-5p并上调RASGEF1B的表达，circDHPR能够抑制HCC的生长和转移，RASGEF1B也被认为是Ras/MAPK信号通路的抑制剂。异常的circDHPR表达会导致细胞增殖的无法控制、肿瘤发生和转移。circDHPR可以作为HCC的生物标志物和治疗靶点。© 2023.Springer Nature Switzerland AG.

Circular RNAs (circRNAs) are noncoding RNAs. Accumulating evidence suggests that circRNAs play a critical role in human biological processes, especially tumorigenesis, and development. However, the exact mechanisms of action of circRNAs in hepatocellular carcinoma (HCC) remain unclear.Bioinformatic tools and RT-qPCR were used to identify the role of circDHPR, a circRNA derived from the dihydropteridine reductase (DHPR) locus, in HCC and para-carcinoma tissues. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the correlation between circDHPR expression and patient prognosis. Lentiviral vectors were used to establish stable circDHPR-overexpressing cells. In vitro and in vivo studies have shown that tumor proliferation and metastasis are affected by circDHPR. Mechanistic assays, including Western blotting, immunohistochemistry, dual-luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation, have demonstrated the molecular mechanism underlying circDHPR.CircDHPR was downregulated in HCC, and low circDHPR expression was associated with poor overall survival and disease-free survival rates. CircDHPR overexpression inhibits tumor growth and metastasis in vitro and in vivo. Further systematic studies revealed that circDHPR binds to miR-3194-5p, an upstream regulator of RASGEF1B. This endogenous competition suppresses the silencing effect of miR-3194-5p. We confirmed that circDHPR overexpression inhibited HCC growth and metastasis by sponging miR-3194-5p to upregulate the expression of RASGEF1B, which is regarded as a suppressor of the Ras/MAPK signaling pathway.Aberrant circDHPR expression leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. CircDHPR may serve as a biomarker and therapeutic target for HCC.© 2023. Springer Nature Switzerland AG.