title: Knock-down of methylenetetrahydrofolate reductase reduces gastric cancer cell survival: an in vitro study.
abstract: The present study aimed to investigate the effect of knocking-down methylenetetrahydrofolate reductase (MTHFR) on the survival of the human gastric cancer cell line MKN45. Antisense and small interfering RNA (siRNA) plasmids were used to target MTHFR in MKN45. Meanwhile, we also constructed a wild-type MTHFR plasmid to assess the effect of over-expression of this protein on cell viability. The knock-down of MTHFR decreased cell survival by approximately 30% compared to the control and resulted in cell cycle arrest at the G2 phase. These cells also had lower levels of c-myc compared to control cells, while over-expression of MTHFR increased cell proliferation and induced the down-regulation of p21WAF1 and hMLH1. Inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells and suggests that MTHFR inhibition may be a novel anticancer approach.
authors.affiliation: Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Sun
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Weng
authors.forename: Ying-Xuan
authors.initials: YX
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000070957:MutL Protein Homolog 1