Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
Biochem Pharmacol. 2024 May;223:116153. doi: 10.1016/j.bcp.2024.116153. Epub 2024 Mar 19.
Hepatocellular carcinoma (HCC), the most common form of primary liver cancers, accounts for a significant portion of cancer-related death globally. However, the molecular mechanisms driving the onset and progression of HCC are still not fully understood. Emerging evidence has indicated that non-protein-coding regions of genomes could give rise to transcripts, termed non-coding RNA (ncRNA), forming novel functional driving force for aberrant cellular activity. Over the past decades, overwhelming evidence has denoted involvement of a complex array of molecular function of ncRNAs at different stages of HCC tumorigenesis and progression. In this context, several pre-clinical studies have highlighted the potentials of ncRNAs as novel therapeutic modalities in the management of human HCC. Moreover, N-methyladenosine (mA) modification, the most prevalent form of internal mRNA modifications in mammalian cells, is essential for the governance of biological processes within cells. Dysregulation of mA in ncRNAs has been implicated in human carcinogenesis, including HCC. In this review, we will discuss dysregulation of several hallmark ncRNAs (miRNAs, lncRNAs, and circRNAs) in HCC and address the latest advances for their involvement in the onset and progression of HCC. We also focus on dysregulation of mA modification and various mA regulators in the etiology of HCC. In the end, we discussed the contemporary preclinical and clinical application of ncRNA-based and mA-targeted therapies in HCC.
肝细胞癌 (HCC) 是原发性肝癌中最常见的形式，占全球癌症相关死亡的很大一部分。然而，驱动 HCC 发生和进展的分子机制仍不完全清楚。新出现的证据表明，基因组的非蛋白编码区域可以产生转录本，称为非编码 RNA (ncRNA)，形成异常细胞活动的新的功能驱动力。在过去的几十年中，大量证据表明 ncRNA 在 HCC 肿瘤发生和进展的不同阶段具有复杂的分子功能。在这种情况下，几项临床前研究强调了 ncRNA 作为人类 HCC 管理中新的治疗方式的潜力。此外，N6-甲基腺苷 (mA) 修饰是哺乳动物细胞中最普遍的 mRNA 内部修饰形式，对于细胞内生物过程的调控至关重要。ncRNA 中的 mA 失调与人类癌症发生有关，包括 HCC。在这篇综述中，我们将讨论 HCC 中几种标志性 ncRNA（miRNA、lncRNA 和 circRNA）的失调，并探讨它们在 HCC 发生和进展中的最新研究进展。我们还重点讨论了 mA 修饰和各种 mA 调节剂在 HCC 发病机制中的失调。最后，我们讨论了基于 ncRNA 和 mA 靶向治疗在 HCC 中的当代临床前和临床应用。
