Mutations in 3'-long terminal repeat of HERV-W family in chromosome 7 upregulate syncytin-1 expression in urothelial cell carcinoma of the bladder through interacting with c-Myb.
Oncogene
; 33(30): 3947-58, 2014 Jul 24.
Article
in En
| MEDLINE
| ID: mdl-24013223
ABSTRACT
Human endogenous retrovirus (HERV) accounts for â¼8% of the human genome. Recent studies have reported that multiple HERV genes and long terminal repeats (LTRs) are involved in human tumorigenesis. Here we demonstrated that HERV-W env (syncytin-1) was overexpressed in 75.6% (62/82) of urothelial cell carcinoma (UCC) tissues of the bladder compared with only 6.1% (5/82) of matched tumor-adjacent tissues (P<0.001). Syncytin-1 overexpression increased proliferation and viability of immortalized human uroepithelial cells. Colony-formation experiments and in-vivo tumor xenografts suggested that syncytin-1 overexpression had oncogenic potential. Syncytin-1 3'-LTR mutations (142T>C and 277A>G) were present in 87.8% (72/82) of UCC tissues. Normal 3'-LTR was found in 12.2% (10/82) of UCC tissues compared with 95.1% (78/82) of matched tumor-adjacent tissues (P<0.001). Interestingly, 3'-LTR mutations were significantly associated with syncytin-1 overexpression. Luciferase assay and expression analysis revealed that 3'-LTR mutations, especially the 142T>C mutation, enhanced the syncytin-1 promoter activity and expression. In-silico analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated the binding of c-Myb to 3'-LTRs when the mutations occurred. This alternative interaction was found to be dependent on 142T>C mutation. C-Myb activated syncytin-1 promoter activity and expression by binding to mutant 3'-LTRs. Taken together, these data indicate that syncytin-1 overexpression may be an indicator of UCC risk. The 3'-LTR mutations may upregulate syncytin-1 expression, enabling it to participate in UCC tumorigenesis and development by interacting with c-Myb.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Proteins
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Urinary Bladder Neoplasms
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Chromosomes, Human, Pair 7
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Carcinoma, Transitional Cell
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Gene Products, env
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Endogenous Retroviruses
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Proto-Oncogene Proteins c-myb
Limits:
Animals
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2014
Document type:
Article
Affiliation country:
China