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miR-211 的下调参与黑色素瘤细胞中黑色素瘤优先表达抗原的表达。

Downregulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma in melanoma cells.

机构信息

Department of Tumor Biology, Division of Bioscience, Center for Advanced Medical Science, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.

出版信息

Int J Oncol. 2011 Sep;39(3):665-72. doi: 10.3892/ijo.2011.1084. Epub 2011 Jun 16.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs whose aberrations are involved in the initiation and progression of human cancers. To seek unique miRNAs contributing to melanoma tumorigenesis, we investigated the global miRNA expression profile of 7 melanoma cell lines and 3 primary cultures of neonatal human epidermal melanocytes (NHEMs) using the stem-loop real-time PCR method. We found 7 miRNAs that were commonly downregulated and 18 that were upregulated in all of the melanoma cell lines in comparison with the 3 primary cultures of NHEMs. We focused on one commonly downregulated miRNA (miR-211), and analyzed its relationship to the expression of preferentially expressed antigen of melanoma (PRAME) protein, which is a potential target of miR-211. We found that all melanoma cell lines exhibited marked down--regulation of miR-211 and upregulation of PRAME mRNA/protein expression in comparison with NHEMs (P<0.05). A significant inverse correlation between miR-211 and PRAME protein expression was found in melanoma cell lines and primary cultures of NHEMs (correlation coefficient of -0.733, P<0.05). We demonstrated that overexpression of miR-211 induced a reduction of PRAME protein levels, and confirmed the target specificity between miR-211 and PRAME by luciferase reporter assay. These results suggest that downregulation of miR-211 may be partly involved in aberrant expression of the PRAME protein in melanoma cells.

摘要

微小 RNA(miRNA)是小的非编码 RNA,其异常参与了人类癌症的发生和发展。为了寻找有助于黑色素瘤发生的独特 miRNA,我们采用茎环实时 PCR 法,研究了 7 株黑色素瘤细胞系和 3 株新生人表皮黑素细胞(NHEM)原代培养物的全球 miRNA 表达谱。与 3 株 NHEM 原代培养物相比,我们发现 7 种 miRNA 普遍下调,18 种 miRNA 上调。我们关注一个普遍下调的 miRNA(miR-211),并分析其与黑色素瘤优先表达抗原(PRAME)蛋白表达的关系,PRAME 蛋白是 miR-211 的潜在靶标。我们发现与 NHEM 相比,所有黑色素瘤细胞系均表现出 miR-211 的明显下调和 PRAME mRNA/蛋白表达的上调(P<0.05)。在黑色素瘤细胞系和 NHEM 原代培养物中,miR-211 与 PRAME 蛋白表达之间存在显著的负相关(相关系数为-0.733,P<0.05)。我们证明了 miR-211 的过表达诱导了 PRAME 蛋白水平的降低,并通过荧光素酶报告基因检测证实了 miR-211 和 PRAME 之间的靶特异性。这些结果表明,miR-211 的下调可能部分参与了黑色素瘤细胞中 PRAME 蛋白的异常表达。

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