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Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression
Evidence has indicated that lysine methyltransferase 2B (KMT2B), a major H3K4 tri-methyltransferase (H3K4me3), contributes to the development of various cancers; however, its role in cervical cancer (CC) is unclear. In this study, increased KMT2B expression was observed in human CC specimens and sig...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760441/ https://www.ncbi.nlm.nih.gov/pubmed/36594087 http://dx.doi.org/10.7150/ijbs.72381 |
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author | Zhao, Dan Yuan, Hui Fang, Yuan Gao, Jian Li, Huimin Li, Mengge Cong, Hui Zhang, Chenglin Liang, Yiyi Li, Jin Yang, Hancao Yao, Ming Du, Min Tu, Hong Gan, Yu |
author_facet | Zhao, Dan Yuan, Hui Fang, Yuan Gao, Jian Li, Huimin Li, Mengge Cong, Hui Zhang, Chenglin Liang, Yiyi Li, Jin Yang, Hancao Yao, Ming Du, Min Tu, Hong Gan, Yu |
author_sort | Zhao, Dan |
collection | PubMed |
description | Evidence has indicated that lysine methyltransferase 2B (KMT2B), a major H3K4 tri-methyltransferase (H3K4me3), contributes to the development of various cancers; however, its role in cervical cancer (CC) is unclear. In this study, increased KMT2B expression was observed in human CC specimens and significantly associated with poor prognosis. The condition medium of KMT2B-overexpressing cells facilitated angiogenesis in vitro. In the subcutaneous model of human CC, KMT2B overexpression significantly promoted tumor growth and increased tumor vascular density. Meanwhile, KMT2B enhanced the migration and invasion of CC cells and promoted their metastasis to bone in a tail-vein-metastasis model. Mechanistically, the genes upregulated by KMT2B were significantly enriched in PI3K-AKT pathway. Using H3K4me3 ChIP-seq analysis, we found increased H3K4me3 level at EGF promoter region in KMT2B-overexpressing HeLa cells. ChIP-qPCR experiments not only confirmed the increased H3K4me3 level of EGF promoter but also determined that in KMT2B-overexpressing HeLa cells, KMT2B increased binding with the EGF promoter. Blocking EGFR diminished the KMT2B-induced PI3K-AKT signaling activation and CC cell migration and invasion. Moreover, EGFR inhibitors abolished the KMT2B-drived tube formation capacity of HUVECs. In conclusion, KMT2B facilitates CC metastasis and angiogenesis by upregulating EGF expression, and may serve as a new therapeutic target for CC. |
format | Online Article Text |
id | pubmed-9760441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-97604412023-01-01 Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression Zhao, Dan Yuan, Hui Fang, Yuan Gao, Jian Li, Huimin Li, Mengge Cong, Hui Zhang, Chenglin Liang, Yiyi Li, Jin Yang, Hancao Yao, Ming Du, Min Tu, Hong Gan, Yu Int J Biol Sci Research Paper Evidence has indicated that lysine methyltransferase 2B (KMT2B), a major H3K4 tri-methyltransferase (H3K4me3), contributes to the development of various cancers; however, its role in cervical cancer (CC) is unclear. In this study, increased KMT2B expression was observed in human CC specimens and significantly associated with poor prognosis. The condition medium of KMT2B-overexpressing cells facilitated angiogenesis in vitro. In the subcutaneous model of human CC, KMT2B overexpression significantly promoted tumor growth and increased tumor vascular density. Meanwhile, KMT2B enhanced the migration and invasion of CC cells and promoted their metastasis to bone in a tail-vein-metastasis model. Mechanistically, the genes upregulated by KMT2B were significantly enriched in PI3K-AKT pathway. Using H3K4me3 ChIP-seq analysis, we found increased H3K4me3 level at EGF promoter region in KMT2B-overexpressing HeLa cells. ChIP-qPCR experiments not only confirmed the increased H3K4me3 level of EGF promoter but also determined that in KMT2B-overexpressing HeLa cells, KMT2B increased binding with the EGF promoter. Blocking EGFR diminished the KMT2B-induced PI3K-AKT signaling activation and CC cell migration and invasion. Moreover, EGFR inhibitors abolished the KMT2B-drived tube formation capacity of HUVECs. In conclusion, KMT2B facilitates CC metastasis and angiogenesis by upregulating EGF expression, and may serve as a new therapeutic target for CC. Ivyspring International Publisher 2023-01-01 /pmc/articles/PMC9760441/ /pubmed/36594087 http://dx.doi.org/10.7150/ijbs.72381 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Zhao, Dan Yuan, Hui Fang, Yuan Gao, Jian Li, Huimin Li, Mengge Cong, Hui Zhang, Chenglin Liang, Yiyi Li, Jin Yang, Hancao Yao, Ming Du, Min Tu, Hong Gan, Yu Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title | Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title_full | Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title_fullStr | Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title_full_unstemmed | Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title_short | Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression |
title_sort | histone methyltransferase kmt2b promotes metastasis and angiogenesis of cervical cancer by upregulating egf expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760441/ https://www.ncbi.nlm.nih.gov/pubmed/36594087 http://dx.doi.org/10.7150/ijbs.72381 |
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