Tembe Varsha, Schramm Sarah-Jane, Stark Mitchell S, Patrick Ellis, Jayaswal Vivek, Tang Yue Hang, Barbour Andrew, Hayward Nicholas K, Thompson John F, Scolyer Richard A, Yang Yee Hwa, Mann Graham J
Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Pigment Cell Melanoma Res. 2015 May;28(3):254-66. doi: 10.1111/pcmr.12343. Epub 2015 Jan 5.
The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh-frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR-150-5p, miR-142-3p and miR-142-5p. Co-analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR-150-5p and the miR-142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets.
微小RNA（miRNA）在黑色素瘤中的作用尚不清楚。我们检测了新鲜冷冻的转移性黑色素瘤中的整体miRNA表达谱，并将其与临床结果和BRAF突变相关联，同时在独立的肿瘤和血清队列中进行验证。我们整合了来自相同样本的miRNA和mRNA信息，并阐明了与结果和突变相关的网络。miR-150-5p、miR-142-3p和miR-142-5p与预后的关联得到了重复验证。miRNA和mRNA的联合分析揭示了一个与预后不良（PP）相关的网络，该网络出人意料地有利于表达与肿瘤发生相反的miRNA。这些miRNA可能是对致癌驱动因素的一种自动调节反应的一部分，而不是驱动因素本身。miR-150-5p和miR-142双链体与良好预后和早期转移性黑色素瘤的强烈关联支持了它们作为生物标志物的潜力。以自动调节方式与PP相关联而过度表达的miRNA不适合作为治疗靶点。
