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Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis
OBJECTIVE: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. METHODS: Two cell sublines with low- and high-metastasis potent...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology; Japan Society of Gynecologic Oncology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627750/ https://www.ncbi.nlm.nih.gov/pubmed/37417299 http://dx.doi.org/10.3802/jgo.2023.34.e71 |
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author | Yi, Jiani Wu, Mengting Zheng, Zhihong Zhou, Qing Li, Xufan Lu, Yan Liu, Pengyuan |
author_facet | Yi, Jiani Wu, Mengting Zheng, Zhihong Zhou, Qing Li, Xufan Lu, Yan Liu, Pengyuan |
author_sort | Yi, Jiani |
collection | PubMed |
description | OBJECTIVE: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. METHODS: Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. RESULTS: There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. CONCLUSION: Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients. |
format | Online Article Text |
id | pubmed-10627750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology; Japan Society of Gynecologic Oncology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106277502023-11-07 Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis Yi, Jiani Wu, Mengting Zheng, Zhihong Zhou, Qing Li, Xufan Lu, Yan Liu, Pengyuan J Gynecol Oncol Original Article OBJECTIVE: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. METHODS: Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. RESULTS: There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. CONCLUSION: Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients. Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology; Japan Society of Gynecologic Oncology 2023-06-27 /pmc/articles/PMC10627750/ /pubmed/37417299 http://dx.doi.org/10.3802/jgo.2023.34.e71 Text en © 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Yi, Jiani Wu, Mengting Zheng, Zhihong Zhou, Qing Li, Xufan Lu, Yan Liu, Pengyuan Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title | Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title_full | Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title_fullStr | Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title_full_unstemmed | Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title_short | Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis |
title_sort | integrated analysis of dna methylome and transcriptome reveals sfrp1 and lipg as potential drivers of ovarian cancer metastasis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627750/ https://www.ncbi.nlm.nih.gov/pubmed/37417299 http://dx.doi.org/10.3802/jgo.2023.34.e71 |
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