ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2023; 19(1):34-49. doi:10.7150/ijbs.72381 This issue Cite
Research Paper
Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression
1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2. Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan Province, China.
3. Department of Orthopedics, Changzheng Hospital, Naval Medical University, 415 Fengyang road, Shanghai, China.
# Present address: Department of Thoracic Surgery, Cancer Research Center, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
† Present address: Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
*These authors contributed equally to this work.
Citation:
Zhao D, Yuan H, Fang Y, Gao J, Li H, Li M, Cong H, Zhang C, Liang Y, Li J, Yang H, Yao M, Du M, Tu H, Gan Y. Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. Int J Biol Sci 2023; 19(1):34-49. doi:10.7150/ijbs.72381. https://www.ijbs.com/v19p0034.htm
Other stylesAbstract
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.
Keywords: cervical cancer, KMT2B, angiogenesis, metastasis, EGF
Citation styles
APA
Zhao, D., Yuan, H., Fang, Y., Gao, J., Li, H., Li, M., Cong, H., Zhang, C., Liang, Y., Li, J., Yang, H., Yao, M., Du, M., Tu, H., Gan, Y. (2023). Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. International Journal of Biological Sciences, 19(1), 34-49. https://doi.org/10.7150/ijbs.72381.
ACS
Zhao, D.; Yuan, H.; Fang, Y.; Gao, J.; Li, H.; Li, M.; Cong, H.; Zhang, C.; Liang, Y.; Li, J.; Yang, H.; Yao, M.; Du, M.; Tu, H.; Gan, Y. Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. Int. J. Biol. Sci. 2023, 19 (1), 34-49. DOI: 10.7150/ijbs.72381.
NLM
Zhao D, Yuan H, Fang Y, Gao J, Li H, Li M, Cong H, Zhang C, Liang Y, Li J, Yang H, Yao M, Du M, Tu H, Gan Y. Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. Int J Biol Sci 2023; 19(1):34-49. doi:10.7150/ijbs.72381. https://www.ijbs.com/v19p0034.htm
CSE
Zhao D, Yuan H, Fang Y, Gao J, Li H, Li M, Cong H, Zhang C, Liang Y, Li J, Yang H, Yao M, Du M, Tu H, Gan Y. 2023. Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. Int J Biol Sci. 19(1):34-49.
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