title: RASSF10 is epigenetically inactivated and induces apoptosis in lung cancer cell lines.
abstract: Ras-association domain family 10 (RASSF10), the latest member of the RASSF family with Ras effector function, has been frequently inactivated by aberrant promoter hypermethylation in several human cancers. However, its role in lung cancer has remained unclear. In this study, we investigated the methylation status of RASSF10 by combined bisulfate restriction analysis (COBRA) and examined its preliminary function in lung cancer cell lines. RASSF10 was methylated in four out of six lung cancer cell lines, including NCI-H157, NCI-460, SPCA-1 and NCI-H446. Treatment with a DNA methylation inhibitor, 5-aza-2'-deoxycytiding (5-aza-DC), restored RASSF10 mRNA expression and the restoration of RASSF10 increased cell apoptosis in a dose dependent manner, whereas knockdown of RASSF10 improved cell proliferation ability and inhibited cell apoptosis rate significantly. Immunofluorescence revealed that RASSF10 protein was located in the cell membrane. Taken together, our data for the first time demonstrates the frequent epigenetic inactivation of RASSF10 in lung cancer cell lines. RASSF10 induces cell apoptosis and might function as a tumor suppressor gene in lung cancer.
authors.affiliation: First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning Province, China.
authors.forename: Yanfu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning Province, China; Chifeng City Hospital, 024000 Chifeng, Inner Mongolia Autonomous Region, China.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Ma
authors.affiliation: First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning Province, China; Ankang City Central Hospital, 725000 Ankang, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Pathology, Dalian Medical University, 116044 Dalian, Liaoning Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, Dalian Medical University, 116044 Dalian, Liaoning Province, China.
authors.forename: Caihua
authors.initials: C
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning Province, China. Electronic address: dlgaomingyang@126.com.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C548440:RASSF10 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine
keywords: COBRA; Lung cancer; Methylation; RASSF10