Microrna profiling analysis of differences between the melanoma of young adults and older adults.
Microrna profiling analysis of differences between the melanoma of young adults and older adults.
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DOI：
10.1186/1479-5876-8-27
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发表时间：
2010-03-19
影响因子：
7.4
通讯作者：
Panelli MC
中科院分区：
文献类型：
--
作者：
Jukic DM;Rao UN;Kelly L;Skaf JS;Drogowski LM;Kirkwood JM;Panelli MC
这项研究首次尝试对青年和老年人群中原发皮肤黑素细胞肿瘤的microRNAs(MiRNAs)的代际差异进行分析。这些数据强调了这些主要调控因子在黑素细胞肿瘤转录机制中的重要性，并表明这些miRs的不同表达水平可能有助于不同年龄黑素细胞肿瘤的表型和病理表现的差异。用低密度microRNA阵列对10例老年人和10例年轻人的福尔马林固定石蜡包埋组织(FFPE)中的666个miR进行了探索性的miRNA分析，其中包括生物学意义不明的传统黑色素瘤和黑素细胞肿瘤。以年龄匹配的良性黑色素细胞痣作为对照。60岁以上的原发性黑色素瘤患者的特点是miRs表达增加，调控TLR-MyD88-NF-kappaB通路(hsa-miR-199a)、RAS/RAB22A通路(hsa-miR-204)、生长分化和迁移(hsa-miR337)、上皮间充质转化(let-7b，hsa-miR-10b/10b*)、侵袭和转移(hsa-miR-10b/10b*)、hsa-miR-30a/e*、hsa-miR-29c*；侵袭性胞质分裂(hsa-miR-99b*)与年轻患者黑色素瘤的比较。与色素痣对照组相比，MIR-211的表达显著下调，随着年龄的增长而降低，是与转移过程相关的MIR之一。青壮年黑色素瘤hsa-miR-449a表达增加，hsa-miR-146b、hsa-miR-214表达降低。MIR-30a*在临床I-II期，成人和儿童黑色素瘤可以预测两个极端年龄组的黑色素瘤组织的分类。虽然病例数量不多，但两个年龄组的阳性淋巴结状态的特征是hsa-miR-30a*和hsa-miR-204的表达具有统计学意义(F检验，p值为0.001)。我们的发现虽然是初步的，但支持这样的观点，即极端年龄的黑色素瘤的差异生物学部分是由microRNA表达的放松调控和已知调节细胞周期、炎症、上皮-间充质转化(EMT)/间质以及更具体地说黑色素瘤中已知改变的基因的miR的微调驱动的。我们的分析显示，miR表达的差异创造了经常受到影响的生物过程的独特模式，清楚地区分了老年和年轻的黑色素瘤。这是对黑素细胞肿瘤在两个极端年龄的微核的一种新的表征，并确定了潜在的诊断和临床病理生物标记物，可能在黑色素瘤的诊断和治疗中作为新的基于miR的靶向手段。
This study represents the first attempt to perform a profiling analysis of the intergenerational differences in the microRNAs (miRNAs) of primary cutaneous melanocytic neoplasms in young adult and older age groups. The data emphasize the importance of these master regulators in the transcriptional machinery of melanocytic neoplasms and suggest that differential levels of expressions of these miRs may contribute to differences in phenotypic and pathologic presentation of melanocytic neoplasms at different ages. An exploratory miRNA analysis of 666 miRs by low density microRNA arrays was conducted on formalin fixed and paraffin embedded tissues (FFPE) from 10 older adults and 10 young adults including conventional melanoma and melanocytic neoplasms of uncertain biological significance. Age-matched benign melanocytic nevi were used as controls. Primary melanoma in patients greater than 60 years old was characterized by the increased expression of miRs regulating TLR-MyD88-NF-kappaB pathway (hsa-miR-199a), RAS/RAB22A pathway (hsa-miR-204); growth differentiation and migration (hsa-miR337), epithelial mesenchymal transition (EMT) (let-7b, hsa-miR-10b/10b*), invasion and metastasis (hsa-miR-10b/10b*), hsa-miR-30a/e*, hsa-miR-29c*; cellular matrix components (hsa-miR-29c*); invasion-cytokinesis (hsa-miR-99b*) compared to melanoma of younger patients. MiR-211 was dramatically downregulated compared to nevi controls, decreased with increasing age and was among the miRs linked to metastatic processes. Melanoma in young adult patients had increased expression of hsa-miR-449a and decreased expression of hsa-miR-146b, hsa-miR-214*. MiR-30a* in clinical stages I-II adult and pediatric melanoma could predict classification of melanoma tissue in the two extremes of age groups. Although the number of cases is small, positive lymph node status in the two age groups was characterized by the statistically significant expression of hsa-miR-30a* and hsa-miR-204 (F-test, p-value < 0.001). Our findings, although preliminary, support the notion that the differential biology of melanoma at the extremes of age is driven, in part, by deregulation of microRNA expression and by fine tuning of miRs that are already known to regulate cell cycle, inflammation, Epithelial-Mesenchymal Transition (EMT)/stroma and more specifically genes known to be altered in melanoma. Our analysis reveals that miR expression differences create unique patterns of frequently affected biological processes that clearly distinguish old age from young age melanomas. This is a novel characterization of the miRnomes of melanocytic neoplasms at two extremes of age and identifies potential diagnostic and clinico-pathologic biomarkers that may serve as novel miR-based targeted modalities in melanoma diagnosis and treatment.
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影响因子：
6.5
作者：
Glud, Martin;Klausen, Mikkel;Drzewiecki, Krzysztof T.
通讯作者：
Drzewiecki, Krzysztof T.
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
DOI：
10.1073/pnas.0404432101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Calin, GA;Liu, CG;Croce, CM
通讯作者：
Croce, CM
影响因子：
5.8
作者：
Bleyer, Archie;Viny, Aaron;Barr, Ronald
通讯作者：
Barr, Ronald
肝细胞癌转移相关microRNA的鉴定
影响因子：
13.5
作者：
Budhu, Anuradha;Jia, Hu-Liang;Wang, Xin Wei
通讯作者：
Wang, Xin Wei