背景：环状RNA（circRNA）在肿瘤进展中扮演着至关重要的角色。Circ-CCT3是一种特别丰富的circRNA，被认为参与了肿瘤发生。然而，circ-CCT3在肝细胞癌中的作用仍不明确。 方法：在这里，通过circRNA微阵列检测并用qRT-PCR验证了circ-CCT3（一种源自CCT3基因外显子3、4和5的circRNA，hsa_circ_0004680）。进行RNA免疫共沉淀（RIP）以确认ALKBH5和METTL3与circ-CCT3的结合。使用甲基化RNA免疫共沉淀（MeRIP）检测circ-CCT3的N6-甲基腺苷（m 2A）水平。进行体内沉淀、荧光素酶报告基因实验、生物素偶联的microRNA捕获和原位荧光杂交等实验，评估circ-CCT3与miR-378a-3p之间的相互作用。评估circ-CCT3在体内外的HCC中的功能。 结果：我们证明circ-CCT3在HCC中高度表达，暗示着肿瘤预后不佳。circ-CCT3表达在HCC患者的总生存中作为独立的危险因素。抑制circ-CCT3的表达抑制了HCC细胞的增殖、侵袭、迁移和HUVEC的血管生成。在机制上，ALKBH5和METTL3可以结合并调节circ-CCT3的mA修饰。进一步地，circ-CCT3通过海绵miR-378a-3p上调FLT-1的表达。 结论：circ-CCT3在HCC中显著上调，并通过miR-378a-3p-FLT1轴促进肝癌发展。同时发现circ-CCT3受ALKBH5和METTL3介导的mA修饰控制。我们的研究强调了circ-CCT3作为HCC治疗的潜在治疗靶标，为circRNA在HCC进展中的机制提供了新的认识。

Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive.Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo.Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p.Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.