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.
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.
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RNA 结合基序、单链相互作用蛋白 3 的下调以及核 HIF1A 的上调与胃癌患者的不良预后相关
DOI：
10.18632/oncotarget.13605
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发表时间：
2017-01-03
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
Wu Y;Yun D;Zhao Y;Wang Y;Sun R;Yan Q;Zhang S;Lu M;Zhang Z;Lu D;Li Y
3号染色体短臂多个区域的缺失在包括胃癌在内的多种肿瘤中存在。RNA结合基序，单链相互作用蛋白3（RBMS 3）是位于该区域的肿瘤抑制基因，介导肿瘤血管生成。然而，RBMS 3在GC中的作用仍不清楚。为了评估RBMS 3和HIF 1A（另一种血管生成的关键调节因子）是否预测GC预后，首先通过定量PCR（qPCR）和western blot检测27例新鲜冷冻GC和配对正常胃组织的RBMS 3和HIF 1A水平，然后通过免疫组织化学（IHC）检测191例GC和46例正常对照的RBMS 3和HIF 1A水平。并采用单因素和多因素分析其与微血管密度（MVD）及临床预后的相关性。为了进一步鉴定RBMS 3的体外功能，采用细胞增殖试验、克隆形成试验、流式细胞术分析和内皮细胞管形成试验。我们发现胃癌患者RBMS 3水平降低，而HIF 1A水平升高。此外，我们证明RBMS 3是一个独立的预后因素，RBMS 3和HIF 1A的水平与GC血管生成和组织病理学分化相关：RBMS 3水平较低和核HIF 1A表达较高的患者预后较差。此外，功能获得和丧失研究揭示了RBMS 3对体外人脐静脉内皮细胞（HUVEC）的G1/S进程、细胞增殖和管状形成的调节。这些发现表明RBMS 3和核HIF 1A可以作为GC的预后生物标志物和治疗靶点。
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.
DOI：
10.1021/jp300525n
发表时间：
2012-06-14
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Zhu J;Martinez-Yamout M;Cardoso R;Yan J;Love RA;Grodsky N;Brooun A;Dyson HJ
通讯作者：
Dyson HJ