Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations

Cancers

Tobias Busche¹  Jörn Kalinowski¹  Anna L. Höving²  Johannes F. W. Greiner²  Kaya E. Witte²  Christian Kaltschmidt²  Barbara Kaltschmidt²  Beatrice A. Windmöller²  Laureen P. Helweg²  Thomas Noll³  Oliver Hertel³  Morris Beshay⁴  Matthias Simon⁴  Cornelius Knabbe⁴  Fritz Mertzlufft⁴  Jesco Pfitzenmaier⁴  Constanze Banz-Jansen⁴ 

[1] Center for Biotechnology-CeBiTec, University of Bielefeld, Universitätsstrasse 27, 33699 Bielefeld, Germany;Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, 33699 Bielefeld, Germany;Department of Cell Culture Technology, Faculty of Technology, University of Bielefeld, Universitätsstrasse 25, 33699 Bielefeld, Germany;Forschungsverbund BioMedizin Bielefeld, OWL (FBMB e.V.), Maraweg 21, 33699 Bielefeld, Germany;

关键词: cancer stem cells;    endometrioid carcinoma;    glioblastoma multiforme;    lung adenocarcinoma;    prostate adenocarcinoma;    nanopore sequencing;   

DOI  :  10.3390/cancers13051136

来源: DOAJ

【 摘 要 】

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

【 授权许可】

Unknown