Wozniak Michal, Czyz Malgorzata
Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
Front Mol Biosci. 2023 May 31;10:1170026. doi: 10.3389/fmolb.2023.1170026. eCollection 2023.
Melanoma is the most lethal skin cancer with increasing incidence worldwide. Despite a great improvement of diagnostics and treatment of melanoma patients, this disease is still a serious clinical problem. Therefore, novel druggable targets are in focus of research. EZH2 is a component of the PRC2 protein complex that mediates epigenetic silencing of target genes. Several mutations activating EZH2 have been identified in melanoma, which contributes to aberrant gene silencing during tumor progression. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are molecular "address codes" for EZH2 silencing specificity, and targeting lncRNAs-EZH2 interaction may slow down the progression of many solid cancers, including melanoma. This review summarizes current knowledge regarding the involvement of lncRNAs in EZH2-mediated gene silencing in melanoma. The possibility of blocking lncRNAs-EZH2 interaction in melanoma as a novel therapeutic option and plausible controversies and drawbacks of this approach are also briefly discussed.
黑色素瘤是最致命的皮肤癌，在全球范围内发病率不断上升。尽管黑色素瘤患者的诊断和治疗有了很大改善，但这种疾病仍然是一个严重的临床问题。因此，新型可药物作用靶点成为研究重点。EZH2是PRC2蛋白复合物的一个组成部分，介导靶基因的表观遗传沉默。在黑色素瘤中已鉴定出几种激活EZH2的突变，这在肿瘤进展过程中导致异常的基因沉默。新出现的证据表明，长链非编码RNA（lncRNAs）是EZH2沉默特异性的分子“地址码”，靶向lncRNAs-EZH2相互作用可能会减缓包括黑色素瘤在内的许多实体癌的进展。本综述总结了目前关于lncRNAs参与黑色素瘤中EZH2介导的基因沉默的知识。还简要讨论了在黑色素瘤中阻断lncRNAs-EZH2相互作用作为一种新型治疗选择的可能性以及这种方法可能存在的争议和缺点。
