Universität zu Köln

Baumert, Hannah Maria, Metzger, Eric, Fahrner, Matthias ORCID: 0000-0001-7955-2518, George, Julie, Thomas, Roman K., Schilling, Oliver ORCID: 0000-0001-7678-7653 and Schuele, Roland (2020). Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death. Cancer Cell Int., 20 (1). LONDON: BMC. ISSN 1475-2867

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Abstract

Background Lung cancer is the leading cause of cancer related death worldwide. Over the past 15 years no major improvement of survival rates could be accomplished. The recently discovered histone methyltransferase KMT9 that acts as epigenetic regulator of prostate tumor growth has now raised hopes of enabling new cancer therapies. In this study, we aimed to identify the function of KMT9 in lung cancer. Methods We unraveled the KMT9 transcriptome and proteome in A549 lung adenocarcinoma cells using RNA-Seq and mass spectrometry and linked them with functional cell culture, real-time proliferation and flow cytometry assays. Results We show that KMT9 alpha and -beta subunits of KMT9 are expressed in lung cancer tissue and cell lines. Importantly, high levels of KMT9 alpha correlate with poor patient survival. We identified 460 genes that are deregulated at the RNA and protein level upon knock-down of KMT9 alpha in A549 cells. These genes cluster with proliferation, cell cycle and cell death gene sets as well as with subcellular organelles in gene ontology analysis. Knock-down of KMT9 alpha inhibits lung cancer cell proliferation and induces non-apoptotic cell death in A549 cells. Conclusions The novel histone methyltransferase KMT9 is crucial for proliferation and survival of lung cancer cells harboring various mutations. Small molecule inhibitors targeting KMT9 therefore should be further examined as potential milestones in modern epigenetic lung cancer therapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Baumert, Hannah Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Fahrner, Matthias UNSPECIFIED orcid.org/0000-0001-7955-2518 UNSPECIFIED George, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Roman K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schilling, Oliver UNSPECIFIED orcid.org/0000-0001-7678-7653 UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-344696
DOI:	10.1186/s12935-020-1141-2
Journal or Publication Title:	Cancer Cell Int.
Volume:	20
Number:	1
Date:	2020
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1475-2867
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN; GENE; EXPRESSION; METHYLATION; SURFACTANT; MUTATIONS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34469