Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC has high rates of death and recurrence, as well as very low survival rates. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNAs, and circRNAs are a class of circular noncoding RNAs that are generated by back-splicing and they modulate multiple functions in a variety of cellular processes. Although the carcinogenesis of HCC is complex, emerging evidence has indicated that m6A modification and circRNA play vital roles in HCC development and progression. However, the underlying mechanisms governing HCC, their cross-talk, and clinical implications have not been fully elucidated. Therefore, in this paper, we elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the m6A modification process. Additionally, we dissected the functional roles of circRNAs in various malignant behaviors of HCC, thereby contributing to HCC initiation, progression and relapse. Furthermore, we demonstrated the cross-talk and interplay between m6A modification and circRNA by revealing the effects of the collaboration of circRNA and m6A modification on HCC progression. Finally, we proposed the clinical potential and implications of m6A modifiers and circRNAs as diagnostic biomarkers and therapeutic targets for HCC diagnosis, treatment and prognosis evaluation.

中文翻译：

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m6A修饰和circRNA在肝细胞癌中的功能作用、交互作用和临床意义

肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。HCC具有高死亡率和复发率，以及非常低的存活率。N6-甲基腺苷 (m6A) 是真核 RNA 中最丰富的修饰，而 circRNA 是一类通过反向剪接产生的环状非编码 RNA，它们在多种细胞过程中调节多种功能。尽管 HCC 的致癌作用很复杂，但新出现的证据表明 m6A 修饰和 circRNA 在 HCC 的发展和进展中起着至关重要的作用。然而，控制 HCC 的潜在机制、它们的交叉对话和临床意义尚未完全阐明。因此，在本文中，我们通过说明 m6A 修饰过程的三种不同调节因子（“writer”、“eraser”和“reader”）阐明了 m6A 修饰在 HCC 癌变中的生物学功能和分子机制。此外，我们剖析了 circRNA 在 HCC 各种恶性行为中的功能作用，从而有助于 HCC 的发生、进展和复发。此外，我们通过揭示 circRNA 和 m6A 修饰的协作对 HCC 进展的影响，证明了 m6A 修饰和 circRNA 之间的串扰和相互作用。最后，我们提出了 m6A 修饰剂和 circRNA 作为 HCC 诊断、治疗和预后评估的诊断生物标志物和治疗靶点的临床潜力和意义。从而促进 HCC 的发生、进展和复发。此外，我们通过揭示 circRNA 和 m6A 修饰的协作对 HCC 进展的影响，证明了 m6A 修饰和 circRNA 之间的串扰和相互作用。最后，我们提出了 m6A 修饰剂和 circRNA 作为 HCC 诊断、治疗和预后评估的诊断生物标志物和治疗靶点的临床潜力和意义。从而促进 HCC 的发生、进展和复发。此外，我们通过揭示 circRNA 和 m6A 修饰的协作对 HCC 进展的影响，证明了 m6A 修饰和 circRNA 之间的串扰和相互作用。最后，我们提出了 m6A 修饰剂和 circRNA 作为 HCC 诊断、治疗和预后评估的诊断生物标志物和治疗靶点的临床潜力和意义。