Center for Medical Research and Innovation of Pudong Hospital, and Intelligent Medicine Institute, Shanghai Medical College, Fudan University, 131 Dongan Road, Shanghai, 200032, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China.
Commun Biol. 2024 Jul 6;7(1):824. doi: 10.1038/s42003-024-06488-9.
The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.
miRNA 的表达失调已在癌症发展过程中被广泛报道，但其中的潜在机制在很大程度上仍未得到解答。在本研究中，我们对全基因组 DNA 甲基化、拷贝数变异和 miRNA 表达数据进行了系统的综合分析，以鉴定低级别胶质瘤中 miRNA 失调的潜在机制。我们确定了 719 个 miRNA，其表达与拷贝数变异或启动子甲基化的改变相关。综合多组学分析揭示了具有不同预后的四个亚型。这些神经胶质瘤亚型表现出不同的免疫相关特征以及临床和遗传特征。通过构建 miRNA 调控网络，我们确定了与免疫逃逸和免疫治疗反应相关的候选 miRNA。最后，通过体外实验验证了 8 个与预后相关的 miRNA，这些 miRNA 通过促进细胞迁移、侵袭和增殖来发挥作用。我们的研究揭示了 DNA 甲基化、拷贝数变异和 miRNA 表达在胶质瘤免疫调节中的相互作用，这对于患者分层和免疫治疗方法生物标志物的开发具有重要意义。
