A novel miR-451a isomiR, associated with amelanotypic phenotype, acts as a tumor suppressor in melanoma by retarding cell migration and invasion.
A novel miR-451a isomiR, associated with amelanotypic phenotype, acts as a tumor suppressor in melanoma by retarding cell migration and invasion.
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DOI：
10.1371/journal.pone.0107502
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dadras SS
中科院分区：
文献类型：
--
作者：
Babapoor S;Fleming E;Wu R;Dadras SS
miRNA 是参与黑色素瘤肿瘤发生关键步骤的关键调控小非编码 RNA；然而，miRNA 5' 或 3' 末端的序列特异性变异 (isomiR) 与癌症表型之间的关系仍不清楚。深度测序和 qRT-PCR 显示，与普通痣和正常皮肤相比，发育不良痣、原位黑色素瘤和侵袭性黑色素瘤中 miR-144/451a 簇和最丰富的 isomiR (miR451a.1) 的表达降低 (n = 101)。 miRNA 原位杂交可重复证实，与痣细胞或邻近角质形成细胞相比，黑色素瘤中 miR-451a.1 丢失。 miR-451a.1 的显着较高表达与黑色素瘤中的无黑色素表型相关 (n = 47)。相反，miR-451a与黑色素表型、表皮内黑色素细胞缺乏佩吉样分散、浅表扩散组织学亚型和肿瘤炎症相关。使用细胞质黑色素梯度（浅色、中色到深色）对培养的黑色素细胞中的 miRNA 进行测序，结果显示 miR-451a 不存在，同时揭示了其他黑色素相关 miRNA，例如 miRNA。深色中的 miR-30b、miR-100 和 miR-590 以及浅至中度色素培养的黑素细胞中的 let-7a、let-7i 和 let-7f。黑色素瘤细胞系中 miR-144/451a 的异位表达导致成熟 miR-451a.1 水平显着高于 miR451a 或 miR-144；并以葡萄糖敏感的方式显着延缓细胞迁移并抑制侵袭。令人惊讶的是，这些效应并不是由钙结合蛋白 39 (CAB39)（一种已证实的 miR451a 基因靶标）介导的。 miR-144/miR-451a 簇是一个新的 miRNA 位点，在黑色素瘤中具有肿瘤抑制活性。
miRNAs are key regulatory small non-coding RNAs involved in critical steps of melanoma tumorigenesis; however, the relationship between sequence specific variations at the 5′ or 3′ termini (isomiR) of a miRNA and cancer phenotype remains unclear. Deep-sequencing and qRT-PCR showed reduced expression of miR-144/451a cluster and most abundant isomiR (miR451a.1) in dysplastic nevi, in-situ and invasive melanomas compared to common nevi and normal skin (n = 101). miRNA in situ hybridization reproducibly confirmed lost miR-451a.1 in melanoma compared to nevus cells or adjacent keratinocytes. Significantly higher expression of miR-451a.1 was associated with amelanotic phenotype in melanomas (n = 47). In contrast, miR-451a was associated with melanotic phenotype, absent pagetoid scatter of intraepidermal melanocytes, superficial spreading histological subtype and tumor inflammation. Sequencing miRNAs from cultured melanocytes with cytoplasmic melanin gradient (light, medium to dark) showed absent miR-451a while revealing other melanin-associated miRNAs, e.g. miR-30b, miR-100 and miR-590 in darkly and let-7a, let-7i and let-7f in lightly to moderately pigmented cultured melanocytes. Ectopic expression of miR-144/451a in melanoma cell lines resulted in markedly higher levels of mature miR-451a.1 than miR451a or miR-144; and significantly retarded cell migration and inhibited invasion in a glucose-sensitive manner. Surprisingly, these effects were not mediated by calcium binding protein 39 (CAB39), a proven miR451a gene target. miR-144/miR-451a cluster is a novel miRNA locus with tumor suppressive activity in melanoma.
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影响因子：
3.7
作者：
Ma Z;Swede H;Cassarino D;Fleming E;Fire A;Dadras SS
通讯作者：
Dadras SS
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
DOI：
10.1385/1-59259-137-x:061
发表时间：
2001-01-01
期刊：
Methods in molecular medicine
影响因子：
--
作者：
M, D;Brooks, S A
通讯作者：
Brooks, S A
DOI：
10.1016/j.bbrc.2007.10.077
发表时间：
2007-12-21
影响因子：
3.1
作者：
Masaki, Shizuka;Ohtsuka, Rie;Umemura, Tsukuru
通讯作者：
Umemura, Tsukuru
影响因子：
1.7
作者：
Doeden, Katie;Ma, Zhihai;Dadras, Soheil S.
通讯作者：
Dadras, Soheil S.