Wu Xiaohong, Gao Yue, Bu Jianlong, Deng Lin, Zhang Pinyi, Chi Meng, Jiang Lihua, Shi Xiaoding, Ning Shangwei, Wang Guonian
Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Front Genet. 2020 Dec 9;11:602035. doi: 10.3389/fgene.2020.602035. eCollection 2020.
There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.
DNA甲基化与长链非编码RNA(lncRNA)的表达之间存在关联,也被称为lncRNA表达定量性状甲基化(lnc-eQTMs)。lnc-eQTMs可能会诱导多种致癌途径。然而,lnc-eQTMs尚未被全面鉴定和研究,它们在肺腺癌(LUAD)和肺鳞癌(LUSC)中的作用在很大程度上尚不清楚。在本研究中,我们在LUAD和LUSC中鉴定了一些位于长链基因间非编码RNA(lincRNAs)和其他类型lncRNAs基因中的差异甲基化位点。建立了一个综合流程,以构建LUAD和LUSC中lnc-eQTMs的两个全局癌症特异性调控网络。eQTMs之间的关联在LUAD和LUSC之间显示出共同和特定的特征。一些lnc-eQTMs也与LUAD和LUSC特异性调控网络中的生存相关。通过功能分析,lnc-eQTMs与癌症相关功能有关,如肺上皮发育和血管生成。药物重新利用分析表明,这些lnc-eQTMs可能介导一些麻醉相关药物在LUAD和LUSC中的作用。总之,本研究阐明了lnc-eQTMs在LUAD和LUSC中的作用,这有助于我们对肺癌发病机制的理解并促进治疗。