MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells.
MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells.
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DOI：
10.1186/1479-5876-9-30
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发表时间：
2011-03-22
影响因子：
7.4
通讯作者：
Nakao K
中科院分区：
文献类型：
--
作者：
Matsushima K;Isomoto H;Yamaguchi N;Inoue N;Machida H;Nakayama T;Hayashi T;Kunizaki M;Hidaka S;Nagayasu T;Nakashima M;Ujifuku K;Mitsutake N;Ohtsuru A;Yamashita S;Korpal M;Kang Y;Gregory PA;Goodall GJ;Kohno S;Nakao K
食管鳞状细胞癌（ESCC）通常在晚期才被诊断出来，直到无法治愈。microRNA（miR）是一种小的非编码RNA，主要通过翻译抑制负调控基因表达。越来越多的证据表明miR的失调与包括ESCC在内的人类恶性肿瘤相关。本研究的目的是寻找在食管鳞癌中特异性表达并发挥生物学作用的miR。从ESCC细胞系OE 21和TE 10以及非恶性人食管鳞状细胞系Het-1A中提取总RNA，并进行微阵列分析。通过定量逆转录酶（RT）-PCR方法分析基于综合分析在2种ESCC和Het-1A细胞之间显示显著差异的miR表达水平。然后，对特异性miR进行功能分析，包括细胞增殖、凋亡和Matrigel侵袭以及伤口愈合测定。使用ESCC肿瘤样本和配对的周围非癌组织内镜下获得的，与组织病理学分化的相关性进行了研究与定量RT-PCR。基于miR微阵列分析，有14个miR在2种ESCC细胞和非恶性Het-1A之间显示出显著差异（超过2倍）。在显著改变的miR中，miR-205表达水平仅在所检查的5种ESCC细胞系中高于任何其他类型的恶性细胞系和Het-1A。因此，miR-205可能是食管鳞癌中的特异性miR。通过转染miR-205前体或抗miR-205抑制剂来调节miR-205的表达并不影响ESCC细胞的增殖和凋亡，但发现miR-205参与细胞侵袭和迁移。Western blot显示，ESCC细胞中miR-205表达的敲低显著增强了锌指E-box结合同源异型盒2的表达，伴随着上皮间质转化调节因子E-cadherin的减少。miR-205的表达水平与食管鳞癌的组织分化程度无关。这些结果表明，miR-205是一种ESCC特异性miR，其通过靶向ZEB 2发挥肿瘤抑制活性和EMT抑制作用。
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC. These results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.
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影响因子：
11.2
作者：
Ohashi S;Natsuizaka M;Wong GS;Michaylira CZ;Grugan KD;Stairs DB;Kalabis J;Vega ME;Kalman RA;Nakagawa M;Klein-Szanto AJ;Herlyn M;Diehl JA;Rustgi AK;Nakagawa H
通讯作者：
Nakagawa H
影响因子：
4.2
作者：
Kimura, Sotai;Naganuma, Seiji;Itoh, Hiroshi
通讯作者：
Itoh, Hiroshi
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
11.2
作者：
Gandellini, Paolo;Folini, Marco;Zaffaroni, Nadia
通讯作者：
Zaffaroni, Nadia
影响因子：
3.7
作者：
Lee, Kuen-Haur;Goan, Yih-Gang;Lu, Pei-Jung
通讯作者：
Lu, Pei-Jung