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LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer
OBJECTIVE: LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance an...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126133/ https://www.ncbi.nlm.nih.gov/pubmed/33992120 http://dx.doi.org/10.1186/s13048-021-00807-y |
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author | Feng, Li-yuan Huang, Yong-zhi Zhang, Wei Li, Li |
author_facet | Feng, Li-yuan Huang, Yong-zhi Zhang, Wei Li, Li |
author_sort | Feng, Li-yuan |
collection | PubMed |
description | OBJECTIVE: LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. METHODS: Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. RESULTS: CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. CONCLUSION: LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-021-00807-y. |
format | Online Article Text |
id | pubmed-8126133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81261332021-05-17 LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer Feng, Li-yuan Huang, Yong-zhi Zhang, Wei Li, Li J Ovarian Res Research OBJECTIVE: LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. METHODS: Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. RESULTS: CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. CONCLUSION: LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-021-00807-y. BioMed Central 2021-05-15 /pmc/articles/PMC8126133/ /pubmed/33992120 http://dx.doi.org/10.1186/s13048-021-00807-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Feng, Li-yuan Huang, Yong-zhi Zhang, Wei Li, Li LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title_full | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title_fullStr | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title_full_unstemmed | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title_short | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
title_sort | lama3 dna methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126133/ https://www.ncbi.nlm.nih.gov/pubmed/33992120 http://dx.doi.org/10.1186/s13048-021-00807-y |
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