title: C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes.
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 C2ORF4 0 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.
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology; Ministry of Education; Shandong University School of Medicine; Jinan, Shandong, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Mingxin
authors.initials: M
authors.lastname: Wen
authors.forename: Yurong
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiuquan
authors.initials: X
authors.lastname: He
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Li
authors.forename: Andres
authors.initials: A
authors.lastname: Castellanos-Martin
authors.forename: Mar
authors.initials: M
authors.lastname: Abad
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Cruz-Hernandez
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Rodriguez
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Losada
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Guangwei
authors.initials: G
authors.lastname: Wei
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018816:Genes, cdc; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology*; D011379:Prognosis; D025521:Tumor Suppressor Proteins
chemical_list: C476999:ECRG4 protein, human; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins
keywords: C2ORF40; DNA methylation; breast cancer; metastasis; mitosis; proliferation