دورية أكاديمية
أعرض في EDS

Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death.

التفاصيل البيبلوغرافية
العنوان: Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death.
المؤلفون: Baumert HM; 1Klinik für Urologie und Zentrale Klinische Forschung, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Universitätsklinikum Freiburg, Freiburg, Germany., Metzger E; 1Klinik für Urologie und Zentrale Klinische Forschung, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Universitätsklinikum Freiburg, Freiburg, Germany., Fahrner M; 2Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; 3Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.; 4Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, Freiburg, Germany., George J; 5Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany., Thomas RK; 5Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.; 6Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany.; 7German Cancer Research Center, German Cancer Consortium (DKTK), Heidelberg, Germany., Schilling O; 2Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Deutsches Konsortium für Translationale Krebsforschung, Standort Freiburg, Freiburg, Germany.; 9BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany., Schüle R; 1Klinik für Urologie und Zentrale Klinische Forschung, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Universitätsklinikum Freiburg, Freiburg, Germany.; Deutsches Konsortium für Translationale Krebsforschung, Standort Freiburg, Freiburg, Germany.; 9BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.; 10CIBSS Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.; K-metics GmbH, Freiburg, Germany.
المصدر: Cancer cell international [Cancer Cell Int] 2020 Feb 17; Vol. 20, pp. 52. Date of Electronic Publication: 2020 Feb 17 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101139795 Publication Model: eCollection Cited Medium: Print ISSN: 1475-2867 (Print) Linking ISSN: 14752867 NLM ISO Abbreviation: Cancer Cell Int Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مستخلص: 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 KMT9α and -β subunits of KMT9 are expressed in lung cancer tissue and cell lines. Importantly, high levels of KMT9α correlate with poor patient survival. We identified 460 genes that are deregulated at the RNA and protein level upon knock-down of KMT9α 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 KMT9α 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.
Competing Interests: Competing interestsThe authors declare that they have no competing interests.
(© The Author(s) 2020.)
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فهرسة مساهمة: Keywords: A549; Epigenetics; Histone methyltransferase; KMT9; Lung cancer; Non-small cell lung cancer; Proteomics; Transcriptomics
تواريخ الأحداث: Date Created: 20200226 Latest Revision: 20220413
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7027090
DOI: 10.1186/s12935-020-1141-2
PMID: 32095117
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2867
DOI:10.1186/s12935-020-1141-2