Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt.
Biotechnology and Biomolecular Chemistry Program, Faculty of Science, Cairo University, Giza 12613, Egypt.
Int J Mol Sci. 2023 Nov 18;24(22):16484. doi: 10.3390/ijms242216484.
Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged as a new paradigm shift in oncology. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have provided a new source of hope for patients with advanced HCC. Yet, the eligibility criteria of HCC patients for ICIs are still a missing piece in the puzzle. Circular RNAs (circRNAs) have recently emerged as a new class of non-coding RNAs that play a fundamental role in cancer pathogenesis. Structurally, circRNAs are resistant to exonucleolytic degradation and have a longer half-life than their linear counterparts. Functionally, circRNAs possess the capability to influence various facets of the tumor microenvironment, especially at the HCC tumor-immune synapse. Notably, circRNAs have been observed to control the expression of immune checkpoint molecules within tumor cells, potentially impeding the therapeutic effectiveness of ICIs. Therefore, this renders them potential cancer-immune biomarkers for diagnosis, prognosis, and therapeutic regimen determinants. In this review, the authors shed light on the structure and functional roles of circRNAs and, most importantly, highlight the promising roles of circRNAs in HCC immunomodulation and their potential as promising biomarkers and immunotherapeutic regimen determinants.
肝细胞癌（HCC）是一种高度致命的恶性肿瘤，治疗选择有限，复发率高。最近，免疫治疗药物，如免疫检查点抑制剂（ICI），在肿瘤学领域出现了新的范式转变。ICI，如程序性死亡蛋白 1（PD-1）抑制剂，为晚期 HCC 患者提供了新的希望。然而，HCC 患者接受 ICI 的资格标准仍然是一个尚未解决的问题。环状 RNA（circRNA）最近作为一类新的非编码 RNA 出现，在癌症发病机制中发挥着重要作用。从结构上看，circRNA 对核酸外切酶的降解具有抗性，其半衰期比线性 RNA 长。从功能上看，circRNA 具有影响肿瘤微环境各个方面的能力，特别是在 HCC 肿瘤免疫突触。值得注意的是，circRNA 被观察到控制肿瘤细胞内免疫检查点分子的表达，可能会阻碍 ICI 的治疗效果。因此，它们成为潜在的癌症免疫生物标志物，用于诊断、预后和治疗方案的决定。在这篇综述中，作者阐述了 circRNA 的结构和功能作用，最重要的是，强调了 circRNA 在 HCC 免疫调节中的有前途的作用及其作为有前途的生物标志物和免疫治疗方案决定因素的潜力。
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