Expression level of microRNA-200c is associated with cell morphology in vitro and histological differentiation through regulation of ZEB1/2 and E-cadherin in gastric carcinoma.
Expression level of microRNA-200c is associated with cell morphology in vitro and histological differentiation through regulation of ZEB1/2 and E-cadherin in gastric carcinoma.
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MicroRNA-200C的表达水平通过调节胃癌中的Zeb1/2和E-钙粘着蛋白的调节与细胞形态和组织学分化有关。
DOI：
10.3892/or.2017.6093
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发表时间：
2018-01
期刊：
影响因子：
4.2
通讯作者：
Kuroda M
中科院分区：
文献类型：
--
作者：
Kurata A;Yamada M;Ohno SI;Inoue S;Hashimoto H;Fujita K;Takanashi M;Kuroda M
硬癌型胃癌以低分化腺癌细胞弥漫浸润为特征，预后差。尽管已经报道了低分化组织学与E-cadherin表达减少的相关性，以及microRNA（miR）-200c通过调节ZEB 1/2与E-cadherin的相关性，但miR-200 c在胃癌发生中的参与尚未完全了解。我们使用了6个来源于胃癌的细胞系，并通过qRT-PCR研究了miR-200 c沿着其靶mRNA ZEB 1/2和E-cadherin的水平。ZEB 1和E-钙粘蛋白的蛋白表达也通过蛋白质印迹法进行了评估。此外，我们还通过原位杂交检测了97例胃腺癌组织中miR-200 c的表达水平，沿着通过免疫组化检测了ZEB 1和E-cadherin的表达水平。qRT-PCR检测结果显示miR-200 c和ZEB 1的表达水平呈负相关（P<0.05）。具有低miR-200 c和高ZEB 1的细胞系在qRT-PCR和蛋白质印迹中均表现出低E-钙粘蛋白表达，并且表现出梭形形态，与具有高miR-200 c水平的那些细胞系中的圆形细胞形态相反。组织样本中miR-200 c和ZEB 1之间以及ZEB 1和E-cadherin水平之间也存在负相关性（P<0.001）。与具有高miR-200 c表达水平的管状形式的癌症相比，具有低miR-200 c、高ZEB 1和低E-cadherin表达的癌症组织与低分化组织学相关（P<0.001）。我们的数据显示，下调miR-200 c主要通过下调E-cadherin通过上调ZEB 1调节细胞形态，导致胃癌组织学分化不良。
Scirrhous type gastric cancer is characterized by diffuse infiltration of poorly differentiated adenocarcinoma cells and poor prognosis. Although association of poorly differentiated histology with reduction in E-cadherin expression, as well as association of microRNA (miR)-200c with E-cadherin through regulation of ZEB1/2, has been reported, participation of miR-200c in gastric carcinogenesis is not fully understood. We used 6 cell lines originating from gastric cancers, and investigated levels of miR-200c along with its target mRNAs ZEB1/2 and E-cadherin by qRT-PCR. ZEB1 and E-cadherin protein expression was also assessed via western blotting. Furthermore, we investigated the expression levels of miR-200c by in situ hybridization, along with the expression of ZEB1 and E-cadherin by immunohistochemistry, in 97 gastric adenocarcinoma tissues. Inverse correlation between miR-200c and ZEB1 levels were obtained by qRT-PCR in cell lines (P<0.05). Cell lines with low miR-200c and high ZEB1 exhibited low E-cadherin expression in both qRT-PCR and western blotting, and exhibited spindle-shaped morphology, in contrast to round cell morphology in those cell lines with high miR-200c levels. Inverse correlations were also obtained between miR-200c and ZEB1 as well as between ZEB1 and E-cadherin levels in tissue samples (P<0.001). Cancer tissues with low miR-200c, high ZEB1, and low E-cadherin expression were associated with poorly differentiated histology, in contrast to tubular form in cancers with high miR-200c expression levels (P<0.001). Our data revealed that downregulation of miR-200c primarily regulated cell morphology by downregulation of E-cadherin through upregulation of ZEB1, leading to poorly differentiated histology in gastric cancer.
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影响因子：
2.5
作者：
Murai, Toshifumi;Yamada, Suguru;Kodera, Yasuhiro
通讯作者：
Kodera, Yasuhiro
影响因子：
3.7
作者：
Konno-Shimizu M;Yamamichi N;Inada K;Kageyama-Yahara N;Shiogama K;Takahashi Y;Asada-Hirayama I;Yamamichi-Nishina M;Nakayama C;Ono S;Kodashima S;Fujishiro M;Tsutsumi Y;Ichinose M;Koike K
通讯作者：
Koike K
影响因子：
28.5
作者：
Hassan O;Ahmad A;Sethi S;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
4.2
作者：
Ji, Meiying;Lee, Eun Jeoung;Park, Seon Mee
通讯作者：
Park, Seon Mee
影响因子：
7.5
作者：
Romero-Perez, Laura;Angeles Lopez-Garcia, M.;Palacios, Jose
通讯作者：
Palacios, Jose