title: Down regulation of RNA binding motif, single-stranded interacting protein 3, along with up regulation of nuclear HIF1A correlates with poor prognosis in patients with gastric cancer.
abstract: Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear.To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls. Moreover, uni- and multivariate analysis were employed to assess the correlations between their levels and microvessel density (MVD) and clinical prognosis. To further identify RBMS3 function in vitro, cell proliferation assay, clonogenic assay, flow cytometry analysis and endothelial cell tube formation assay were employed.We found that RBMS3 level was decreased, whereas HIF1A was elevated in GC. Furthermore, we demonstrated that RBMS3 was an independent prognostic factor and the levels of RBMS3 and HIF1A were associated with GC angiogenesis and histopathological differentiation: patients with lower RBMS3 level and higher nuclear HIF1A expression had poorer prognosis. Besides, gain- and loss-of-function study revealed RBMS3 regulation on G1/S progression, cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. These findings implicated that RBMS3 and nuclear HIF1A could act as prognostic biomarkers and therapeutic targets for GC.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Youliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Ruochuan
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Shangxin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Mingdian
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C405932:RBMS3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators
keywords: HIF1A; MVD; RBMS3; gastric cancer; prognostic marker