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黑色素瘤中特定微小RNA的表达改变:miRNA-155的抗增殖和促凋亡活性

Altered expression of selected microRNAs in melanoma: antiproliferative and proapoptotic activity of miRNA-155.

作者信息

Levati Lauretta, Alvino Ester, Pagani Elena, Arcelli Diego, Caporaso Patrizia, Bondanza Sergio, Di Leva Gianpiero, Ferracin Manuela, Volinia Stefano, Bonmassar Enzo, Croce Carlo Maria, D'Atri Stefania

机构信息

Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, I-00167 Rome, Italy.

出版信息

Int J Oncol. 2009 Aug;35(2):393-400.

Abstract

Altered expression of microRNAs (miRNAs) has been detected in cancer, suggesting that these small non-coding RNAs can act as oncogenes or tumor suppressor genes. In the present study, we investigated the expression of miRNA-17-5p, miRNA-18a, miRNA-20a, miRNA-92a, miRNA-146a, miRNA-146b and miRNA-155 by real-time quantitative RT-PCR in a panel of melanocyte cultures and melanoma cell lines and explored the possible role of miRNA-155 in melanoma cell proliferation and survival. The analyzed miRNAs were selected on the basis of previous studies strongly supporting their involvement in cancer development and/or progression. We found that miRNA-17-5p, miRNA-18a, miRNA-20a, and miRNA-92a were overexpressed, whereas miRNA-146a, miRNA-146b and miRNA-155 were down-regulated in the majority of melanoma cell lines with respect to melanocytes. Ectopic expression of miRNA-155 significantly inhibited proliferation in 12 of 13 melanoma cell lines with reduced levels of this miRNA and induced apoptosis in 4 out of 4 cell lines analyzed. In conclusion, our data further support the finding of altered miRNA expression in melanoma cells and establish for the first time that miRNA-155 is a negative regulator of melanoma cell proliferation and survival.

摘要

在癌症中已检测到微小RNA(miRNA)表达改变,这表明这些小的非编码RNA可作为癌基因或肿瘤抑制基因发挥作用。在本研究中,我们通过实时定量逆转录PCR检测了一组黑素细胞培养物和黑色素瘤细胞系中miRNA-17-5p、miRNA-18a、miRNA-20a、miRNA-92a、miRNA-146a、miRNA-146b和miRNA-155的表达,并探讨了miRNA-155在黑色素瘤细胞增殖和存活中的可能作用。所分析的miRNA是根据先前的研究选择的,这些研究有力地支持了它们参与癌症发生和/或进展。我们发现,与黑素细胞相比,大多数黑色素瘤细胞系中miRNA-17-5p、miRNA-18a、miRNA-20a和miRNA-92a过表达,而miRNA-146a、miRNA-146b和miRNA-155下调。miRNA-155的异位表达显著抑制了13个黑色素瘤细胞系中12个细胞系的增殖,这些细胞系中该miRNA水平降低,并且在所分析的4个细胞系中诱导了4个细胞系的凋亡。总之,我们的数据进一步支持了黑色素瘤细胞中miRNA表达改变的发现,并首次证实miRNA-155是黑色素瘤细胞增殖和存活的负调节因子。

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