Open AccessUNC5D , suppressed by promoter hypermethylation, inhibits cell metastasis by activating death‐associated protein kinase 1 in prostate cancer
Author(s) -
Dong Dong,
Zhang Lufang,
Bai Changsen,
Ma Na,
Ji Wei,
Jia Li,
Zhang Aimin,
Zhang Pengyu,
Ren Li,
Zhou Yunli
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13935
Subject(s) - gene knockdown , ectopic expression , cancer research , metastasis suppressor gene , metastasis suppressor , dna methylation , metastasis , epigenetics , biology , prostate cancer , microarray analysis techniques , cancer , cancer cell , gene expression , cell culture , gene , genetics
Prostate cancer ( PC a) death primarily occurs due to metastasis of the cells, but little is known about the underlying molecular mechanisms. This study aimed to evaluate the expression of UNC 5D , a newly identified tumor suppressor gene, analyze its epigenetic alterations, and elucidate its functional relevance to PC a metastasis. Meta‐analysis of publicly available microarray datasets revealed that UNC 5D expression was frequently downregulated in PC a tissues and inversely associated with PC a metastasis. These results were verified in clinical specimens by real‐time PCR and immunohistochemistry assays. Through methylation analysis, the downregulated expression of UNC 5D in PC a tissues and cell lines was found to be attributable to the hypermethylation of the promoter. A negative correlation was observed between methylation and UNC 5D mRNA expression in PC a samples. The ectopic expression of UNC 5D in PC a cells effectively reduced their ability to migrate and invade both in vitro and in vivo, and si RNA ‐mediated knockdown of UNC 5D yielded consistent results. UNC 5D can recruit and activate death‐associated protein kinase 1, which remained to be essential for its metastatic suppressor function. In conclusion, these results suggested that UNC 5D as a novel putative metastatic suppressor gene that is commonly down‐regulated by hypermethylation in PC a.