Ely Abdullah, Bloom Kristie, Maepa Mohube Betty, Arbuthnot Patrick
Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Hepatocell Carcinoma. 2021 Jan 27;8:1-17. doi: 10.2147/JHC.S268291. eCollection 2021.
After being overlooked for decades, circular RNAs (circRNAs) have recently generated considerable interest. circRNAs play a role in a variety of normal and pathological biological processes, including hepatocarcinogenesis. Many circRNAs contribute to hepatocarcinogenesis through sponging of microRNAs (miRs) and disruption of cellular signaling pathways that play a part in control of cell proliferation, metastasis and apoptosis. In most cases, overexpressed circRNAs sequester miRs to cause de-repressed translation of mRNAs that encode oncogenic proteins. Conversely, low expression of circRNAs has also been described in hepatocellular carcinoma (HCC) and is associated with inhibited production of tumor suppressor proteins. Other functions of circRNAs that contribute to hepatocarcinogenesis include translation of truncated proteins and acting as adapters to regulate influence of transcription factors on target gene expression. circRNAs also affect hepatocyte transformation indirectly. For example, the molecules regulate immune surveillance of cancerous cells and influence the liver fibrosis that commonly precedes HCC. Marked over- or under-expression of circRNA expression in HCC, with correlating plasma concentrations, has diagnostic utility and assays of these RNAs are being developed as biomarkers of HCC. Although knowledge in the field has recently surged, the myriad of described effects suggests that not all may be vital to hepatocarcinogenesis. Nevertheless, investigation of the role of circRNAs is providing valuable insights that are likely to contribute to improved management of a serious and highly aggressive cancer.
在被忽视数十年后，环状RNA（circRNA）最近引起了广泛关注。circRNA在多种正常和病理生物学过程中发挥作用，包括肝癌发生。许多circRNA通过充当微小RNA（miR）的海绵以及破坏参与细胞增殖、转移和凋亡控制的细胞信号通路，从而促进肝癌发生。在大多数情况下，过表达的circRNA会隔离miR，导致编码致癌蛋白的mRNA的翻译去抑制。相反，在肝细胞癌（HCC）中也发现circRNA低表达，这与肿瘤抑制蛋白的产生受抑制有关。circRNA促进肝癌发生的其他功能包括截短蛋白的翻译以及作为衔接子调节转录因子对靶基因表达的影响。circRNA也间接影响肝细胞转化。例如，这些分子调节癌细胞的免疫监视，并影响通常先于HCC出现的肝纤维化。HCC中circRNA表达的显著过表达或低表达以及与之相关的血浆浓度具有诊断价值，针对这些RNA的检测方法正在开发为HCC的生物标志物。尽管该领域的知识最近激增，但众多已描述的作用表明并非所有作用对肝癌发生都至关重要。然而，对circRNA作用的研究正在提供有价值的见解，这可能有助于改善对这种严重且极具侵袭性的癌症的管理。
