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Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer
- Title
- Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer
- Authors
- Ahn, Jinwoo; Kim, Kwang Hyun; Park, Sanghui; Ahn, Young-Ho; Kim, Ha Young; Yoon, Hana; Lee, Ji Hyun; Bang, Duhee; Lee, Dong Hyeon
- Ewha Authors
- 이동현; 윤하나; 박상희; 안영호; 김광현
- SCOPUS Author ID
- 이동현; 윤하나; 박상희; 안영호; 김광현
- Issue Date
- 2016
- Journal Title
- ONCOTARGET
- ISSN
- 1949-2553
- Citation
- ONCOTARGET vol. 7, no. 39, pp. 63252 - 63260
- Keywords
- urinary bladder neoplasm; chromatin remodeling; UTX; UTY; epigenesis
- Publisher
- IMPACT JOURNALS LLC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66.7%). To evaluate the functional roles of UTX and UTY in tumor progression, we designed UTX and UTY single knockout and UTX-UTY double knockout experiments using a CRISPR/Cas9 lentiviral system, and compared the proliferative capacities of two UBC cell lines in vitro. Single UTX or UTY knockout increased cell proliferation as compared to UTX-UTY wild-type cells. UTX-UTY double knockout cells exhibited greater proliferation than single knockout cells. These findings suggest both UTX and UTY function as dose-dependent suppressors of UBC development. While UTX escapes X chromosome inactivation in females, UTY may function as a male homologue of UTX, which could compensate for dosage imbalances.
- DOI
- 10.18632/oncotarget.11207
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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