title: Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer.
abstract: RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor-node-metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5-silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Junich
authors.initials: J
authors.lastname: Ishida
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Goki
authors.initials: G
authors.lastname: Suda
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Muranaka
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C473448:RBM5 protein, human; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020741:rho GTP-Binding Proteins
keywords: Gastric cancer; RNA-binding motif 5; tumor progression; tumor suppressor gene