MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines.
MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines.
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DOI：
10.7150/ijbs.7.133
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发表时间：
2011-01-27
影响因子：
9.2
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Deng Y;Deng H;Bi F;Liu J;Bemis LT;Norris D;Wang XJ;Zhang Q
羧基末端结合蛋白1（CtBP 1）是一种转录辅助抑制因子，抑制多种肿瘤抑制基因的表达。在本研究中，我们确定了miR-137作为黑色素瘤细胞中CtBP 1表达的潜在调节因子。发现miR-137在黑素瘤细胞系中的表达与CtBP 1水平呈负相关。靶扫描预测了CtBP 1 3′非翻译区（3′UTR）内的miR-137推定位点，该位点位于nt 710-716，在物种间高度保守。为了探索miR-137靶向CtBP 1的机制，我们进行了Argonaute 2（Ago 2）-pull down试验，并鉴定了与CtBP 1 mRNA复合的miR-137。miR-137抑制CtBP 1 3' UTR报告酶活性，并且这种作用随着推定的3' UTR靶位点的缺失而丧失。与报告基因测定的结果一致，miR-137的异位表达降低了CtBP 1的表达水平。此外，miR-137的表达增加了CtBP 1的直接下游效应物，如E-cadherin和Bax。人类miR-137基因位于染色体1 p22，先前已确定其为黑色素瘤的抑制区域。这项研究表明，miR-137可能通过直接靶向CtBP 1抑制上皮间质转化（EMT）并诱导黑色素瘤细胞凋亡而发挥肿瘤抑制作用，从而说明miR-137和CtBP 1在黑色素瘤发展中的功能联系。
Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3′ untranslated region (3′UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3' UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3' UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development.
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影响因子：
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通讯作者：
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