Next-generation sequencing reveals a novel role of lysine-specific demethylase 1 in adhesion of rhabdomyosarcoma cells

  • Lysine-specific demethylase 1 (LSD1), a histone lysine demethylase with the main specificity for H3K4me2, has been shown to be overexpressed in rhabdomyosarcoma (RMS) tumor samples. However, its role in RMS biology is not yet well understood. Here, we identified a new role of LSD1 in regulating adhesion of RMS cells. Genetic knockdown of LSD1 profoundly suppressed clonogenic growth in a panel of RMS cell lines, whereas LSD1 proved to be largely dispensable for regulating cell death and short-term survival. Combined RNA and ChIP-sequencing performed to analyze RNA expression and histone methylation at promoter regions revealed a gene set enrichment for adhesion-associated terms upon LSD1 knockdown. Consistently, LSD1 knockdown significantly reduced adhesion to untreated surfaces. Importantly, precoating of the plates with the adhesives collagen I or fibronectin rescued this reduced adhesion of LSD1 knockdown cells back to levels of control cells. Using KEGG pathway analysis, we identified 17 differentially expressed genes (DEGs) in LSD1 knockdown cells related to adhesion processes, which were validated by qRT-PCR. Combining RNA and ChIP-sequencing results revealed that, within this set of genes, SPP1, C3AR1, ITGA10 and SERPINE1 also exhibited increased H3K4me2 levels at their promoter regions in LSD1 knockdown compared to control cells. Indeed, LSD1 ChIP experiments confirmed enrichment of LSD1 at their promoter regions, suggesting a direct transcriptional regulation by LSD1. By identifying a new role of LSD1 in the modulation of cell adhesion and clonogenic growth of RMS cells, these findings highlight the importance of LSD1 in RMS.
Metadaten
Author:Tinka Haydn, Sarah Kehr, Dominica Willmann, Eric Metzger, Roland Schüle, Simone FuldaORCiDGND
URN:urn:nbn:de:hebis:30:3-638219
DOI:https://doi.org/10.1002/ijc.32806
ISSN:1097-0215
Parent Title (English):International journal of cancer
Publisher:Wiley-Liss
Place of publication:Bognor Regis
Document Type:Article
Language:English
Date of Publication (online):2019/11/21
Date of first Publication:2019/11/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/08
Tag:LSD1; cancer treatment; rhabdomyosarcoma
Volume:146
Issue:12
Page Number:15
First Page:3435
Last Page:3449
Note:
This work has been partially supported by grants from the BMBF (to S.F.).
HeBIS-PPN:494705175
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0