Histone Methyltransferases G9a/Ehmt2 and GLP/Ehmt1 Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma

Author:

Souza Barbara Kunzler123,Freire Natalia Hogetop124,Monteiro Thiago Santos3,Herlinger Alice Laschuk12ORCID,Jaeger Mariane124ORCID,Dalmolin Matheus G. S.24,de Farias Caroline Brunetto124,Gregianin Lauro12456,Brunetto André T.124ORCID,Brunetto Algemir L.124,Thiele Carol J.7,Roesler Rafael128ORCID

Affiliation:

1. Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil

2. National Science and Technology Institute for Children’s Cancer Biology and Pediatric Oncology—INCT BioOncoPed, Porto Alegre 90035-003, Brazil

3. Epigenica Biosciences, Canoas 92035-000, Brazil

4. Children’s Cancer Institute, Porto Alegre 90620-110, Brazil

5. Department of Pediatrics, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil

6. Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil

7. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

8. Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil

Abstract

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/Ehmt1 gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types. Herein, we evaluated the role of G9a in two solid pediatric tumors: neuroblastoma (NB) and Ewing sarcoma (ES). Our results show that G9a/Ehmt2 and GLP/Ehmt1 expression is higher in tumors with poorer prognosis, including St4 International Neuroblastoma Staging System (INSS) stage, MYCN amplified NB, and metastatic ES. Importantly, higher G9a and GLP levels were associated with shorter patient overall survival (OS) in both NB and ES. Moreover, pharmacological inhibition of G9a/GLP reduced cell viability in NB and ES cells. These findings suggest that G9a and GLP are associated with more aggressive NB and ES tumors and should be further investigated as being epigenetic targets in pediatric solid cancers.

Funder

National Council for Scientific and Technological Development

Rio Grande do Sul State Research Foundation

Children’s Cancer Institute; the Coordination for the Improvement of Higher Education Personnel

Coordination for the Improvement of Higher Education Personnel

Center for Cancer Research, Intramural Research Program at the National Cancer Institute, National Institutes of Health

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3