Ruijie Wang1, Ya Li2, Peipei Du2, Xiaoan Zhang3, Xiaofu Li4, Guomei Cheng5. 1. 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. 2. Department of Cytopathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 3. Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 4. Department of Cytopathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: lixiaofu1964@hotmail.com. 5. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: guomei69@126.com.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
Authors: Gabriela D A Guardia; Bruna R Correa; Patricia Rosa Araujo; Mei Qiao; Suzanne Burns; Luiz O F Penalva; Pedro A F Galante Journal: NPJ Genom Med Date: 2020-01-16 Impact factor: 8.617
Authors: Yuyou Jiang; Xianqin Zhang; Li Rong; Yi Hou; Jing Song; Wanfeng Zhang; Min He; Yan Xie; Yue Li; Fangzhou Song Journal: Oncol Lett Date: 2021-04-08 Impact factor: 2.967
Authors: Gabriela D A Guardia; Bruna R Correa; Patricia Rosa Araujo; Mei Qiao; Suzanne Burns; Luiz O F Penalva; Pedro A F Galante Journal: NPJ Genom Med Date: 2020-01-16 Impact factor: 8.617