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Abstract
Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2ORF40 mRNA level is significantly associated with patient disease-free survival and distant cancer metastasis. Overexpression of C2ORF40 inhibits breast cancer cell proliferation, migration and invasion. By contrast, silencing C2ORF40 expression promotes these biological phenotypes. Bioinformatics and FACS analysis reveal C2ORF40 functions at G2/M phase by downregulation of mitotic genes expression, including UBE2C. Our results suggest that C2ORF40 acts as a tumor suppressor gene in breast cancer pathogenesis and progression and is a candidate prognostic marker for this disease.
Submitted
01/17/2013
Revised
03/28/2013
Accepted
04/09/2013
Disclosure of Potential Conflicts of Interest
No potential conflict of interest was disclosed.
Acknowledgments
This work was supported by National Natural Science Foundation of China (grant numbers 81172528, 31271461 to G. W.); Doctoral Fund of Ministry of Education of China (grant number 20110131110035 to G. W.); Shandong Provincial Natural Science Foundation, China (grant number ZR2011HM034 to G. W.); by the National Institutes of Health, National Cancer Institute grant (grant number R01 CA116481 to J. H. M.); the Low Dose Scientific Focus Area, Office of Biological and Environmental Research, US Department of Energy (grant number DE-AC02–05CH11231 to J. H. M.); and Laboratory Directed Research and Development Program (LDRD) (to J. H.M.).