Nishimoto Yuki, Murakami Akihiro, Sato Shun, Kajimura Takuya, Nakashima Kengo, Yakabe Kazuyuki, Sueoka Kotaro, Sugino Norihiro
Department of Obstetrics and Gynecology Yamaguchi University Graduate School of Medicine Ube Japan.
Reprod Med Biol. 2018 Jan 25;17(2):173-181. doi: 10.1002/rmb2.12086. eCollection 2018 Apr.
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 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, 10 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.
羰基还原酶1（CBR1）参与癌症进展。最近，作者报道CBR1表达缺失与子宫颈癌预后不良相关。在此，我们研究了CBR1表达降低是否通过诱导上皮间质转化（EMT）促进癌症进展。
将互补DNA的反义构建体（反义克隆）和空载体（对照克隆）转染到人子宫颈鳞状细胞癌细胞系（SKG II和SiHa）中，并在体外分析这些克隆的增殖和EMT标志物表达。在一项体内研究中，将10个反义克隆和对照克隆的细胞皮下注射到裸鼠体内，并观察8周的肿瘤发生情况。
随着CBR1表达降低，反义克隆的增殖增加，同时上皮标志物（E-钙黏蛋白和细胞角蛋白）减少，间充质标志物（纤连蛋白、α-平滑肌肌动蛋白和N-钙黏蛋白）增加，这表明诱导了EMT。在体内研究中，反义组的肿瘤体积明显大于对照组。
CBR1表达降低通过诱导子宫颈鳞状细胞癌中的EMT促进肿瘤生长。
