The involvement of RhoA and Wnt-5a in the tumorigenesis and progression of ovarian epithelial carcinoma.

The involvement of RhoA and Wnt-5a in the tumorigenesis and progression of ovarian epithelial carcinoma.
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RhoA和Wnt-5a参与卵巢上皮癌的发生和进展

DOI:
10.3390/ijms141224187
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发表时间:
2013-12-12
影响因子:
5.6
通讯作者:
Zhao Y
Zhao Y
中科院分区:
生物学2区
文献类型:
--
作者:
Chen S;Wang J;Gou WF;Xiu YL;Zheng HC;Zong ZH;Takano Y;Zhao Y

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Ras同源基因家族成员A (RhoA)参与了wnt -5a诱导的胃癌和乳腺癌细胞的迁移。我们研究了RhoA和Wnt-5a在卵巢癌中的作用。测定正常输卵管上皮、良性肿瘤、原发性卵巢癌和转移性网膜中RhoA和Wnt-5a mRNA和蛋白的表达。利用sirna敲低OVCAR3卵巢癌细胞中的RhoA或Wnt-5a,检测细胞表型和相关分子的表达。RhoA和Wnt-5a mRNA和蛋白在转移网膜中的表达明显高于卵巢癌、良性肿瘤和正常输卵管上皮(p < 0.05),并与卵巢癌的分化和FIGO分期(I/II期vs. III/IV期)呈正相关(p < 0.05)。卵巢癌中RhoA与Wnt-5a表达呈正相关(p = 0.001, R2 = 0.1669)。RhoA或Wnt-5a敲除下调RhoA和Wnt-5a的表达;细胞增殖减少;促进G1阻滞和细胞凋亡;抑制板足形成、细胞迁移和侵袭;降低PI3K、Akt、p70S6k、Bcl-xL、survivin和VEGF mRNA或蛋白的表达。这是首次证明RhoA和Wnt-5a与卵巢癌发生和细胞凋亡抑制有关;RhoA与Wnt-5a表达可能呈正相关。RhoA是卵巢癌中潜在的肿瘤发生、分化和进展的生物标志物。
Ras homolog gene family member A (RhoA) is involved in Wnt-5a–induced migration of gastric and breast cancer cells. We investigated the roles of RhoA and Wnt-5a in ovarian carcinoma. RhoA and Wnt-5a mRNA and protein expression in normal fallopian tube epithelium, benign tumors, primary ovarian carcinomas, and metastatic omentum were quantified. RhoA or Wnt-5a was knocked down in OVCAR3 ovarian carcinoma cells using siRNAs and cell phenotype and expression of relevant molecules were assayed. RhoA and Wnt-5a mRNA and protein expression were found to be significantly higher in metastatic omentum than in ovarian carcinomas, benign tumors, and normal fallopian tube epithelium (p < 0.05), and positively associated with differentiation and FIGO staging (stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). RhoA and Wnt-5a expression were positively correlated in ovarian carcinoma (p = 0.001, R2 = 0.1669). RhoA or Wnt-5a knockdown downregulated RhoA and Wnt-5a expression; reduced cell proliferation; promoted G1 arrest and apoptosis; suppressed lamellipodia formation, cell migration, and invasion; and reduced PI3K, Akt, p70S6k, Bcl-xL, survivin, and VEGF mRNA or protein expression. This is the first demonstration that RhoA and Wnt-5a are associated with ovarian carcinogenesis and apoptosis inhibition; there might be positive correlation between RhoA and Wnt-5a expression. RhoA is a potential tumorigenesis, differentiation, and progression biomarker in ovarian carcinoma.
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