Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Obstetrics and Gynecology, Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China.
Department of Cytopathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Life Sci. 2019 Sep 15;233:116708. doi: 10.1016/j.lfs.2019.116708. Epub 2019 Jul 29.
Cervical cancer seriously affects women's health. The function of methylated alterations in the long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. Our study aims to identify the functional effects of lncRNA methylation in cervical carcinogenesis.
Genome-wide DNA methylation of 6 samples was assessed using the Illumina Infinium MethylationEPIC BeadChip. RNA sequencing (RNA-seq) data and survival follow-up time of 307 samples from The Cancer Genome Atlas (TCGA) dataset were enrolled in this study. The statistical analysis and graphical work were mainly realized by R language.
Methylation map identified 3962 hypermethylated CpG sites and 4484 hypomethylated CpG sites in cervical cancer (|Δβ| ≥ 0.20). Bioinformatic analysis of the lncRNA expression identified 363 upregulated and 664 downregulated lncRNAs with log2 (fold change) ≥ 1.00 in squamous cervical carcinoma (SCC) samples. Weighted gene co-expression network analysis (WGCNA) and Venn diagram revealed that lncRNA MAGI2 antisense RNA 3 (lncRNA MAGI2-AS3), lncRNA WT1 antisense RNA (lncRNA WT1-AS) and lncRNA SOX21 antisense divergent transcript 1 (lncRNA SOX21-AS1) were important methylation changed lncRNAs. Kaplan-Meier survival curves showed only lncRNA SOX21-AS1 had clinical prognostic value in cervical cancer. Gene set enrichment analysis (GSEA) suggest that lncRNA SOX21-AS1 involve in the multiple cellular processes and might significantly suppress cervical tumorigenesis.
These insights into the functional role of lncRNA SOX21-AS1 DNA methylome alterations in cervical cancer might promote clinically new applicable in diagnosis and prognosis.
宫颈癌严重影响女性健康。长链非编码 RNA（lncRNA）中甲基化改变的功能促进了癌症的进展和转移。我们的研究旨在确定 lncRNA 甲基化在宫颈癌发生中的功能影响。
使用 Illumina Infinium MethylationEPIC BeadChip 评估了 6 个样本的全基因组 DNA 甲基化。本研究纳入了来自癌症基因组图谱（TCGA）数据集的 307 个样本的 RNA 测序（RNA-seq）数据和生存随访时间。统计分析和图形工作主要通过 R 语言实现。
甲基化图谱在宫颈癌中鉴定出 3962 个高甲基化 CpG 位点和 4484 个低甲基化 CpG 位点（|Δβ|≥0.20）。lncRNA 表达的生物信息学分析鉴定出在鳞状宫颈癌（SCC）样本中，有 363 个上调和 664 个下调的 lncRNA，其 log2（fold change）≥1.00。加权基因共表达网络分析（WGCNA）和 Venn 图表明，lncRNA MAGI2 反义 RNA 3（lncRNA MAGI2-AS3）、lncRNA WT1 反义 RNA（lncRNA WT1-AS）和 lncRNA SOX21 反义发散转录本 1（lncRNA SOX21-AS1）是重要的甲基化改变的 lncRNA。Kaplan-Meier 生存曲线表明，只有 lncRNA SOX21-AS1 在宫颈癌中具有临床预后价值。基因集富集分析（GSEA）表明，lncRNA SOX21-AS1 参与多种细胞过程，可能显著抑制宫颈癌的发生。
这些关于 lncRNA SOX21-AS1 DNA 甲基化组改变在宫颈癌中的功能作用的见解可能会促进临床上新的诊断和预后应用。
