title: Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.
abstract: Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Nie
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yue
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Cao
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D018389:Codon, Nonsense / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D020868:Gene Silencing / Q000502:physiology*; D006657:Histones / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018389:Codon, Nonsense; D006657:Histones; C542435:MARVELD1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins