MicroRNA miR-125b induces senescence in human melanoma cells

MicroRNA miR-125b induces senescence in human melanoma cells
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DOI:
10.1097/cmr.0b013e328345333b
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发表时间:
2011-06-01
期刊:
影响因子:
2.2
通讯作者:
Gniadecki, Robert
Gniadecki, Robert
中科院分区:
医学4区
文献类型:
--
作者:
Glud, Martin;Manfe, Valentina;Gniadecki, Robert

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microRNA(miRNAs)是一种参与基因调控的非编码RNA小分子。miRNA的异常表达与包括癌症在内的几种疾病的发生或进展有关。在以前的研究中,我们发现,在恶性黑色素瘤淋巴结微转移中,miRNA-125 b(miR-125 b)的表达比非转移性肿瘤低两倍。为了进一步了解miR-125 b的功能作用,我们评估了其过表达或沉默是否会影响黑色素瘤细胞系的凋亡、增殖或衰老。我们发现miR-125 b的过表达诱导了典型的衰老细胞形态,包括胞质/核比增加和胞质β-半乳糖苷酶表达增强。相比之下,抑制miR-125 b导致自发凋亡水平降低30-35%。我们认为,在早期皮肤恶性黑色素瘤中下调miR-125 b可能有助于增加这种肿瘤的转移能力。黑色素瘤研究21:253-256(C)2011年威科健康垂直栏Lippincott威廉姆斯&威尔金斯。
MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melanoma producing lymph node micrometastases than in nonmetastasizing tumors. To get further insight into the functional role of miR-125b, we assessed whether its overexpression or silencing affects apoptosis, proliferation, or senescence in melanoma cell lines. We showed that overexpression of miR-125b induced typical senescent cell morphology, including increased cytoplasmatic/nucleus ratio and intensive cytoplasmatic beta-galactosidase expression. In contrast, inhibition of miR-125b resulted in 30-35% decreased levels of spontaneous apoptosis. We propose that downregulation of miR-125b in an early cutaneous malignant melanoma can contribute to the increased metastatic capability of this tumor. Melanoma Res 21:253-256 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.