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Life Sci. 2019 Sep 15;233:116708. doi: 10.1016/j.lfs.2019.116708. Epub 2019 Jul 29.

Hypomethylation of the lncRNA SOX21-AS1 has clinical prognostic value in cervical cancer.

Author information

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.

KEYWORDS:

Cervical cancer; DNA methylation; Prognosis; lncRNA; lncRNA SOX21-AS1

PMID:
31369759
DOI:
10.1016/j.lfs.2019.116708
[Indexed for MEDLINE]

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