ABSTRACT Glioblastoma (GBM) is the most malignant form of glioma. Glioma stem cells (GSCs) contribute to the initiation, progression, and recurrence of GBM as a result of their self-renewal

potential and tumorigenicity. Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Although CDK8 has been shown to be implicated in the malignancy of several

types of cancer, its functional role and mechanism in gliomagenesis remain largely unknown. Here, we demonstrate how CDK8 plays an essential role in maintaining stemness and tumorigenicity

in GSCs. The genetic inhibition of _CDK8_ by shRNA or CRISPR interference resulted in an abrogation of the self-renewal potential and tumorigenicity of patient-derived GSCs, which could be

correlated with stem cell markers including _c-MYC_ and _SOX2_ in human GBM specimens. Additionally, _CDK8_ expression is associated with poor survival in GBM patients. Collectively, these

findings highlight the importance of the CDK8-c-MYC axis in maintaining stemness and tumorigenicity in GSCs; these findings also identify the CDK8-c-MYC axis as a potential target for

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MCM8 IS REGULATED BY EGFR SIGNALING AND PROMOTES THE GROWTH OF GLIOMA STEM CELLS THROUGH ITS INTERACTION WITH

DNA-REPLICATION-INITIATING FACTORS Article 15 June 2021 CDC42EP3 PROMOTES GLIOMA PROGRESSION VIA REGULATION OF CCND1 Article Open access 01 April 2022 TRANSCRIPTIONAL CDK INHIBITORS, CYC065

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2007;27:6177–82. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We wish to thank Dr. H. Hojo (University of Tokyo) for technical training in

RNA-seq data analysis. RNA-seq data and survival analysis were performed using the super-computing resource provided by Human Genome Center, the Institute of Medical Science, the University

of Tokyo. This work was supported in part by the Japan Society for the Promotion of Science (20H03407 to EH), and the Extramural Collaborative Research Grant of Cancer Research Institute,

Kanazawa University. AUTHOR INFORMATION Author notes * These authors equally contributed: Kazuya Fukasawa, Takuya Kadota, Tetsuhiro Horie AUTHORS AND AFFILIATIONS * Laboratory of

Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan Kazuya Fukasawa, Takuya Kadota, Tetsuhiro Horie, Kazuya Tokumura, Ryuichi Terada, Yuka Kitaguchi,

 Gyujin Park, Shinsuke Ochiai, Sayuki Iwahashi, Yasuka Okayama, Manami Hiraiwa, Takanori Yamada, Takashi Iezaki & Eiichi Hinoi * Drug Discovery Research Department, Kyoto Pharmaceutical

Industries, Ltd, Kyoto, Japan Takuya Kadota, Megumi Yamamoto, Tatsuya Kitao & Hiroaki Shirahase * Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa

University Graduate School, Kanazawa, Ishikawa, Japan Yuka Kitaguchi & Katsuyuki Kaneda * Cell-Bionomics Research Unit, Institute for Frontier Science Initiative, Kanazawa University,

Kanazawa, Ishikawa, Japan Masaharu Hazawa & Richard W. Wong * WPI Nano Life Science Institute (WPI‐Nano LSI), Kanazawa University, Kanazawa, Ishikawa, Japan Richard W. Wong & Atsushi

Hirao * Division of Innovative Cancer Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan Tomoki Todo * Cancer and Stem Cell Research Program, Division of Molecular

Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan Atsushi Hirao * United Graduate School of Drug Discovery and Medical Information Sciences, Gifu

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