title: Frequent down-regulation of hRAB37 in metastatic tumor by genetic and epigenetic mechanisms in lung cancer.
abstract: We looked for the involvement tumor suppressor gene (TSG) in lung cancer in 17q25 region by loss of heterozygosity analysis and 5'/3' RACE and identified a candidate gene named human RAB37 (hRAB37), which encodes a small GTPase. The Ras-GTPase superfamily functions as important regulators including membrane trafficking and cytoskeletal organization. Therefore, we further examined the mRNA expression and promoter/exon1 hypermethylation of hRAB37 gene in paired normal and tumor lung tissue from 71 non-small cell lung cancer (NSCLC) patients. Low hRAB37 mRNA expression occurred in 47.9% (34/71) of patient and promoter/exon1 hypermethylation of hRAB37 was found in 57.7% (41/71) of patients. Low mRNA expression of hRAB37 was significantly associated with their promoter/exon1 hypermethylation. Importantly, a reduction in hRAB37 mRNA expression and promoter/exon1 hypermethylation was found to be significantly associated with lung metastatic patients as compared to non-metastatic patients. 5-Aza-2-deoxycytidine treatment of a highly metastatic cell line showed demethylation and re-expression of the hRAB37 gene and coincided with reduced migration. Knockdown of hRAB37 in low metastasis cell line led to a significant increase in cell migration. Our findings demonstrated that hRAB37 small GTPase and acts as a metastasis-related TSG in lung cancer. Promoter/exon1 methylation is the predominant mechanism in down-regulation of the hRAB37, and can serve as a potential prediction biomarker of NSCLC progression.
authors.affiliation: Institute of Microbiology and Immunology, National Yang Ming University, No. 155, Section 2, Linong Street, Beitou District, Taipei 112, Taiwan, ROC.
authors.forename: Chu-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Ruo-Chia
authors.initials: RC
authors.lastname: Tseng
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
authors.forename: Ming-Ta
authors.initials: MT
authors.lastname: Hsu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics*; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D020691:rab GTP-Binding Proteins