Up-regulated Dicer expression in patients with cutaneous melanoma.
Up-regulated Dicer expression in patients with cutaneous melanoma.
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DOI：
10.1371/journal.pone.0020494
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发表时间：
2011
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：
Ma Z;Swede H;Cassarino D;Fleming E;Fire A;Dadras SS
MicroRNAs(MiRNAs)是一种小的非编码RNA(18-24个核苷酸)，最近被证明在癌症进展过程中调节基因表达。DICER是多组分miRNA生物发生途径中的中心酶，参与将前体miRNAs切割成功能成熟的形式。新的证据表明，在一些人类恶性肿瘤中，Dier的表达被解除了调控，它与肿瘤的进展有关，但这种作用在皮肤癌中还没有被研究过。应用抗人DICER蛋白的单抗和免疫组织化学方法，比较了40 4例临床诊断正常皮肤组织和4 0 4例皮肤肿瘤组织中DICER蛋白的表达，其中包括黑色素细胞痣(n = 71)、多种黑色素瘤(n = 2 2 3)、癌(n = 73)和肉瘤(n = 12)。结果显示，与癌或肉瘤相比，81%的皮肤、80%的肢端样角化性黑色素瘤和96%的转移性黑色素瘤的细胞特异性表达上调(P<；0.0001)。与良性黑色素细胞痣相比，黑色素瘤中DICER的表达显著升高(P<；0.0001)。在皮肤黑色素瘤患者中，DICER表达上调与肿瘤有丝分裂指数(P = 0.04)、Breslow‘s侵袭深度(P = 0.03)、淋巴结转移(P = 0.04)以及美国癌症联合委员会较高的临床分期(P = 0.009)显著相关。通过蛋白质印迹分析，我们证实了体外细胞特异性上调的DICER蛋白。对皮肤肿瘤的mRNA谱进行的汇集分析显示，在皮肤黑色素瘤的RNA水平上，DICER的表达上调，也表明参与规范的miRNAs的生物发生和成熟的其他酶的调控放松。在皮肤黑色素瘤患者中，表达增加可能是临床上有用的生物标志物。为了预测未来黑色素瘤患者对基于miRNA的治疗的易感性，需要了解Dier的放松调控及其对miRNA成熟的影响。
MicroRNAs (miRNAs) are small non-coding RNAs (18–24 nucleotides) that have recently been shown to regulate gene expression during cancer progression. Dicer, a central enzyme in the multi-component miRNA biogenesis pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence shows that Dicer expression is deregulated in some human malignancies and it correlates with tumor progression, yet this role has not yet been investigated in skin cancers. Using an anti-human monoclonal antibody against Dicer and immunohistochemistry, we compared the expression of Dicer protein among 404 clinically annotated controls and skin tumors consisting of melanocytic nevi (n = 71), a variety of melanomas (n = 223), carcinomas (n = 73) and sarcomas (n = 12). Results showed a cell-specific up-regulated Dicer in 81% of cutaneous, 80% of acrolentiginous and 96% of metastatic melanoma specimens compared to carcinoma or sarcoma specimens (P<0.0001). The expression of Dicer was significantly higher in melanomas compared to benign melanocytic nevi (P<0.0001). In patients with cutaneous melanomas, Dicer up-regulation was found to be significantly associated with an increased tumor mitotic index (P = 0.04), Breslow's depth of invasion (P = 0.03), nodal metastasis (P = 0.04) and a higher American Joint Committee on Caner (AJCC) clinical stage (P = 0.009). Using western blot analysis, we confirmed the cell-specific up-regulation of Dicer protein in vitro. A pooled-analysis on mRNA profiling in cutaneous tumors showed up-regulation of Dicer at the RNA level in cutaneous melanoma, also showing deregulation of other enzymes that participate in the biogenesis and maturation of canonical miRNAs. Increased Dicer expression may be a clinically useful biomarker for patients with cutaneous melanoma. Understanding deregulation of Dicer and its influence on miRNA maturation is needed to predict the susceptibility of melanoma patients to miRNA-based therapy in the future.
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影响因子：
3.7
作者：
Jakymiw, Andrew;Patel, Rushi S.;Deming, Natasha;Bhattacharyya, Indraneel;Shah, Priya;Lamont, Richard J.;Stewart, Carol M.;Cohen, Donald M.;Chan, Edward K. L.
通讯作者：
Chan, Edward K. L.
影响因子：
7.4
作者：
Jukic DM;Rao UN;Kelly L;Skaf JS;Drogowski LM;Kirkwood JM;Panelli MC
通讯作者：
Panelli MC
影响因子：
5.7
作者：
Karube, Y;Tanaka, H;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
3.5
作者：
Chiosea, S. I.;Barnes, E. L.;Seethala, R. R.
通讯作者：
Seethala, R. R.
影响因子：
6.5
作者：
Mueller, Daniel W.;Rehli, Michael;Bosserhoff, Anja K.
通讯作者：
Bosserhoff, Anja K.