MicroRNA-193b Represses Cell Proliferation and Regulates Cyclin D1 in Melanoma
MicroRNA-193b Represses Cell Proliferation and Regulates Cyclin D1 in Melanoma
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DOI：
10.2353/ajpath.2010.091061
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发表时间：
2010-05-01
影响因子：
6
通讯作者：
Tron, Victor A.
中科院分区：
文献类型：
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作者：
Chen, Jiamin;Feilotter, Harriet E.;Tron, Victor A.
皮肤黑色素瘤是人类皮肤癌的一种侵袭性形式，其特征是高转移潜力和不良预后。为了更好地了解 microRNA (miRNA) 在黑色素瘤中的作用，我们对良性痣和转移性黑色素瘤的组织样本中的 470 种 miRNA 的表达进行了分析。我们鉴定出 31 个 miRNA 在转移性黑色素瘤中相对于良性痣有差异表达（13 个上调，18 个下调）。值得注意的是，miR-193b 在检查的黑色素瘤组织中显着下调。为了了解 miR-193b 在黑色素瘤中的作用，进行了功能研究。黑色素瘤细胞系中 miR-193b 的过度表达抑制细胞增殖。基因表达谱鉴定出 Malme-3M 细胞中 314 个因 miR-193b 过表达而下调的基因。其中 18 个下调基因，包括细胞周期蛋白 D1 (CCND1)，也被 TargetScan 鉴定为假定的 miR-193b 靶标。 Malme-3M 细胞中 miR-193b 的过表达使 CCND1 mRNA 和蛋白下调 >= 50%。荧光素酶报告基因测定证实，miR-193b 通过与 CCND1 mRNA 的 3'非翻译区结合来直接调节 CCND1。这些研究表明 miR-193b 抑制细胞增殖并调节 CCND1 表达，并表明 miR-193b 的失调可能在黑色素瘤的发展中发挥重要作用。 （Am J Pathol 2010，176：2520-2529；DOI：10.2353/ajpath.2010.091061）
Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. To better understand the role of microRNAs (miRNAs) in melanoma, the expression of 470 miRNAs was profiled in tissue samples from benign nevi and metastatic melanomas. We identified 31 miRNAs that were differentially expressed (13 up-regulated and 18 down-regulated) in metastatic melanomas relative to benign nevi. Notably, miR-193b was significantly down-regulated in the melanoma tissues examined. To understand the role of miR-193b in melanoma, functional studies were undertaken. Overexpression of miR-193b in melanoma cell lines repressed cell proliferation. Gene expression profiling identified 314 genes down-regulated by overexpression of miR-193b in Malme-3M cells. Eighteen of these down-regulated genes, including cyclin D1 (CCND1), were also identified as putative miR-193b targets by TargetScan. Overexpression of miR-193b in Malme-3M cells down-regulated CCND1 mRNA and protein by >= 50%. A luciferase reporter assay confirmed that miR-193b directly regulates CCND1 by binding to the 3'un-translated region of CCND1 mRNA. These studies indicate that miR-193b represses cell proliferation and regulates CCND1 expression and suggest that dysregulation of miR-193b may play an important role in melanoma development. (Am J Pathol 2010, 176:2520-2529; DOI: 10.2353/ajpath.2010.091061)