Department of Dermatology, University Hospital Zürich (USZ), Zürich, Switzerland.
Faculty of Medicine, University of Zürich (UZH), Zürich, Switzerland.
RNA Biol. 2022 Jan;19(1):996-1006. doi: 10.1080/15476286.2022.2110390.
RNA editing refers to non-transient RNA modifications that occur after transcription and prior to translation by the ribosomes. RNA editing is more widespread in cancer cells than in non-transformed cells and is associated with tumorigenesis of various cancer tissues. However, RNA editing can also generate neo-antigens that expose tumour cells to host immunosurveillance. Global RNA editing in melanoma and its relevance to clinical outcome currently remain poorly characterized. The present study compared RNA editing as well as gene expression in tumour cell lines from melanoma patients of short or long metastasis-free survival, patients relapsing or not after immuno- and targeted therapy and tumours harbouring or mutations. Overall, our results showed that gene expression can be a marker of resistance to BRAF and MEK inhibition and gives some insights of candidate genes as potential biomarkers. In addition, this study revealed an increase in Adenosine-to-Inosine editing in Alu regions and in non-repetitive regions, including the hyperediting of the and genes in relapsed tumour samples during targeted therapy and of the gene in NRAS mutated melanoma cells. Therefore, RNA editing could be a promising tool for identifying predictive markers, tumour neoantigens and targetable pathways that could help in preventing relapses during immuno- or targeted therapies.
RNA 编辑是指在核糖体翻译之前转录后发生的非瞬时 RNA 修饰。RNA 编辑在癌细胞中的发生频率高于非转化细胞，与各种癌症组织的肿瘤发生有关。然而，RNA 编辑也可以产生新抗原，使肿瘤细胞暴露于宿主免疫监视之下。目前，全球黑色素瘤中的 RNA 编辑及其与临床结局的相关性仍知之甚少。本研究比较了短或长无转移生存期、免疫和靶向治疗后复发或不复发的黑色素瘤患者、携带 或 突变的肿瘤细胞系中的 RNA 编辑和基因表达。总的来说，我们的结果表明，基因表达可以作为对 BRAF 和 MEK 抑制的耐药性的标志物，并为候选基因作为潜在生物标志物提供了一些见解。此外，这项研究还揭示了在 Alu 区域和非重复区域中腺苷到肌苷的编辑增加，包括在靶向治疗期间复发肿瘤样本中 基因和 基因的超编辑，以及在 NRAS 突变黑色素瘤细胞中 基因的编辑。因此，RNA 编辑可能是一种很有前途的工具，可以识别预测标志物、肿瘤新抗原和可靶向的途径，有助于预防免疫或靶向治疗期间的复发。
