Decreased WWOX expression promotes angiogenesis in osteosarcoma
Decreased WWOX expression promotes angiogenesis in osteosarcoma
复制标题
WWOX表达减少促进骨肉瘤中的血管生成
DOI：
10.18632/oncotarget.17126
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Li Jiaping
中科院分区：
文献类型：
--
作者：
Wen Jia;Xu Zongchao;Li Jiazhen;Zhang Yingqiang;Fan Wenzhe;Wang Yu;Lu Mingjian;Li Jiaping
WWOX（含WW结构域的氧化还原酶）是一种重要的肿瘤抑制因子。在这项研究中，我们使用201例骨肉瘤患者的样本来研究WWOX对血管生成和侵袭的影响。WWOX水平与RUNX2、VEGF水平呈负相关，与OPN水平无相关性。在研究的临床病理特征中，WWOX仅与对新辅助化疗的反应相关，其在骨肉瘤组织中的表达是无病生存的预测因子。WWOX促进体外骨肉瘤细胞凋亡，抑制bcl-2、OPN、RUNX2、VEGF的侵袭和表达。在MG-63细胞中，bcl-2上调VEGF表达，RUNX2上调VEGF和OPN表达。使用DNA甲基化抑制剂可增加MG-63细胞中WWOX的表达，骨肉瘤患者中WWOX基因启动子CpG岛的甲基化与WWOX表达的抑制有关。骨肉瘤细胞中WWOX的过表达抑制了共培养HUVEC细胞的管状形成，高WWOX表达与微血管密度（MVD）降低有关。提示骨肉瘤中WWOX表达降低可抑制细胞凋亡，促进侵袭，增加MVD。
WWOX (WW domain-containing oxidoreductase) is known to be an important tumor suppressor in cancer. In this study, we used samples from 201 osteosarcoma patients to investigate the effects of WWOX on angiogenesis and invasion. WWOX levels were negatively correlated with RUNX2 and VEGF levels, but were not correlated with OPN levels. Among the clinicopathological characteristics examined, WWOX was associated only with response to neoadjuvant chemotherapy, and its expression in osteosarcoma tissues was a predictor of disease-free survival. WWOX promoted apoptosis and inhibited invasion and expression of bcl-2, OPN, RUNX2, and VEGF in osteosarcoma cells in vitro. In MG-63 cells, bcl-2 increased VEGF expression, while RUNX2 increased VEGF and OPN expression. Administration of DNA methylation inhibitors increased WWOX expression in MG-63 cells and methylation of WWOX gene promoter CpG island in the osteosarcoma of patients was associated with suppression of WWOX expression. Overexpression of WWOX in osteosarcoma cells inhibited tube formation in co-cultured HUVEC cells, and high WWOX expression was associated with decreased microvessel density (MVD). These results suggest that reduced WWOX expression in osteosarcoma inhibits apoptosis, promotes invasion and increases MVD.
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影响因子：
11.2
作者：
Croce CM;Reed JC
通讯作者：
Reed JC
DOI：
--
发表时间：
2009-05
期刊：
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
影响因子：
--
作者：
U. Lewandowska;M. Żelazowski;Karolina Seta;Magdalena Byczewska;E. Płuciennik;A. Bednarek
通讯作者：
U. Lewandowska;M. Żelazowski;Karolina Seta;Magdalena Byczewska;E. Płuciennik;A. Bednarek
DOI：
10.12659/msm.896451
发表时间：
2016-05-25
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Lin BC;Huang D;Yu CQ;Mou Y;Liu YH;Zhang DW;Shi FJ
通讯作者：
Shi FJ
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
影响因子：
5.6
作者：
San Martin, Inga A.;Varela, Nelson;Gaete, Marcia;Villegas, Karina;Osorio, Mariana;Tapia, Julio C.;Antonelli, Marcelo;Mancilla, Edna E.;Pereira, Barry P.;Nathan, Saminathan S.;Lian, Jane B.;Stein, Janet L.;Stein, Gary S.;Van Wijnen, Andre J.;Galindo, Mario
通讯作者：
Galindo, Mario