Decreased carbonyl reductase 1 expression promotes tumor growth via epithelial mesenchymal transition in uterine cervical squamous cell carcinomas.

Decreased carbonyl reductase 1 expression promotes tumor growth via epithelial mesenchymal transition in uterine cervical squamous cell carcinomas.
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DOI:
10.1002/rmb2.12086
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发表时间:
2018-04
影响因子:
3.4
通讯作者:
Sugino N
Sugino N
中科院分区:
医学3区
文献类型:
--
作者:
Nishimoto Y;Murakami A;Sato S;Kajimura T;Nakashima K;Yakabe K;Sueoka K;Sugino N

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羰基还原酶1(CBR 1)参与癌症进展。最近,作者报道了CBR 1表达的缺失与宫颈癌的预后不良相关。在这里,我们研究了降低CBR 1表达是否通过诱导上皮间质转化(EMT)促进癌症进展。将CBR 1互补DNA的反义构建体(反义克隆)和空载体(对照克隆)转染人宫颈鳞癌细胞系(SKG II和SiHa),并在体外分析这些克隆的增殖和EMT标志物表达。在体内研究中,将反义克隆和对照克隆的107个细胞皮下注射到裸鼠中,并观察肿瘤发生8周。随着CBR 1表达的减少,反义克隆的增殖增加,伴随着上皮标志物(E-钙粘蛋白和细胞角蛋白)的减少和间充质标志物(纤连蛋白、α-平滑肌肌动蛋白和N-钙粘蛋白)的增加,这表明EMT诱导。在体内研究中,反义组的肿瘤体积显著大于对照组。CBR 1表达降低通过诱导子宫颈鳞状细胞癌EMT促进肿瘤生长
Carbonyl reductase 1 (CBR1) is involved in cancer progression. Recently, the authors reported that the loss of CBR1 expression is associated with a poor prognosis in uterine cervical cancer. Here, we investigated whether the decreased CBR1 expression promotes cancer progression by inducing the epithelial mesenchymal transition (EMT). Antisense constructs of CBR1 complementary DNA (antisense clones) and the empty vectors (control clones) were transfected into human uterine cervical squamous cell carcinoma cell lines (SKG II and SiHa) and the proliferation and EMT marker expression of these clones were analyzed in vitro. In an in vivo study, 107 cells of the antisense and control clones were subcutaneously injected into nude mice and the tumorigenesis was observed for 8 weeks. With the decreased CBR1 expression, the proliferation of the antisense clones increased, accompanied by a decrease in epithelial markers (E‐cadherin and cytokeratin) and an increase in mesenchymal markers (fibronectin, alpha‐smooth muscle actin, and N‐cadherin), which suggests EMT induction. In the in vivo study, the tumor volume in the antisense group was significantly larger than that in the control group. Decreased CBR1 expression promotes tumor growth by inducing EMT in uterine cervical squamous cell carcinomas.
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