期刊
CANCER RESEARCH
卷 74, 期 18, 页码 5103-5117出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-14-0427
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资金
- HMRF grant from the Food and Health Bureau of the Hong Kong Special Administrative Region, China [01120446]
- 973 grant from the Ministry of Science and Technology of China [2014CB964700]
- Research Grants Council (RGC) of the Hong Kong [476310, 476113]
- Private Fund form Dept OG, CUHK
The Protocadherin 10 (PCDH10) is inactivated often by promoter hypermethylation in various human tumors, but its possible functional role as a tumor suppressor gene is not established. In this study, we identify PCDH10 as a novel Wnt pathway regulatory element in endometrioid endometrial carcinoma (EEC). PCDH10 was down-regulated in EEC tumor cells by aberrant methylation of its promoter. Restoring PCDH10 levels suppressed cell growth and triggered apoptosis in EEC cells and tumor xenografts. Gene expression profiling revealed as part of the transcriptomic changes induced by PCDH10 a reduction in levels of MALAT1, a long noncoding RNA, that mediated tumor suppression functions of PCDH10 in EEC cells. We found that MALAT1 transcription was regulated by Wnt/beta-catenin signaling via TCF promoter binding and PCDH10 decreased MALAT1 by modulating this pathway. Clinically, MALAT1 expression was associated with multiple parameters in patients with EEC. Taken together, our findings establish a novel PCDH10-Wnt/beta-catenin-MALAT1 regulatory axis that contributes to EEC development. (C) 2014 AACR.
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