Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2

Author:

Ler Lian Dee123ORCID,Ghosh Sujoy45ORCID,Chai Xiaoran5,Thike Aye Aye6ORCID,Heng Hong Lee12,Siew Ee Yan12ORCID,Dey Sucharita7,Koh Liang Kai12ORCID,Lim Jing Quan12ORCID,Lim Weng Khong12ORCID,Myint Swe Swe12,Loh Jia Liang12,Ong Pauline12ORCID,Sam Xin Xiu6ORCID,Huang Dachuan12,Lim Tony6,Tan Puay Hoon6ORCID,Nagarajan Sanjanaa12,Cheng Christopher Wai Sam8,Ho Henry8,Ng Lay Guat8ORCID,Yuen John8,Lin Po-Hung9ORCID,Chuang Cheng-Keng9ORCID,Chang Ying-Hsu9,Weng Wen-Hui10ORCID,Rozen Steven G.25ORCID,Tan Patrick271112,Creasy Caretha L.13ORCID,Pang See-Tong9ORCID,McCabe Michael T.13ORCID,Poon Song Ling12,Teh Bin Tean12714ORCID

Affiliation:

1. Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore.

2. Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

3. NUS Graduate School for Integrative Sciences and Engineering, 28 Medical Drive, Singapore 117456, Singapore.

4. Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.

5. Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857, Singapore.

6. Department of Pathology, Singapore General Hospital, Singapore, Singapore.

7. Cancer Science Institute of Singapore, National University of Singapore, Centre for Life Sciences, Singapore 117456, Singapore.

8. Department of Urology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.

9. Division of Urooncology, Department of Urology, Chang Gung University and Memorial Hospital at LinKou, TaoYuan, Taiwan.

10. Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan.

11. Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore 169610, Singapore.

12. Genome Institute of Singapore, 60 Biopolis Street Genome, Singapore 138672, Singapore.

13. Cancer Epigenetics Discovery Performance Unit, Oncology R&D, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.

14. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, #07-18, Singapore 138673, Singapore.

Abstract

Bladder cancer with loss of KDM6A expression is vulnerable to inhibition of EZH2.

Funder

Singapore National Medical Research Council

Singapore National Cancer Centre Research Fund

Verdant Foundation

Duke-NUS Medical School

Cancer Science Institute, Singapore

Chang Gung Memorial Hospital

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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