Br J Cancer：miRNA差异表达可能用于黑色素瘤的诊断或预后指标

恶性黑色素瘤的发病率正在逐年上升，并且其上升速度比任何其他癌症都要快。皮肤切除活检仍然是黑色素瘤诊断和预后判断的标准方法。良性和恶性病变组织之间有显著的形态重叠，肿瘤的厚度并不总是一个准确的预测指标。

因此确定新的分子标记物以支持组织学检查非常有必要，近日研究人员对不同病理阶段的福尔马林固定、石蜡包埋的样本进行微陈列分析，以便识别差异表达的微小RNA（miRNA）。相关研究论文发表在British Journal of Cancer杂志上。

采用QRT-PCR验证这些微小RNA的差异表达，miRNA的功能学研究采用黑色素瘤细胞转染能调节miRNA表达的miRNA前体或抑制剂来开展。结果发现有20个miRNA在良性痣和原发性或转移性黑色瘤中存在显著差异性表达，而其中大部分在黑色素瘤中是下调的，而只有2个miRNA即miR-203和miR-205在原发性和转移性黑色素瘤中是差异表达的。

在体外试验中，抑制过度的miR-200C和miR-205能显著抑制黑色素瘤细胞的克隆集落形成能力，抑制过表达miR-211既能集落形成能力，也能抑制黑色素瘤细胞的侵袭。该研究所确定的一系列miRNA差异表达可能用于黑色素瘤的诊断或预后指标，其中3个miRNAs（即miR-200c、miR-205和miR-211）发挥肿瘤抑制基因的功能。

doi:10.1038/bjc.2011.568
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Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors.

Xu Y, Brenn T, Brown ER, Doherty V, Melton DW.

BACKGROUND:

The incidence of malignant melanoma is increasing faster than that for any other cancer. Histological examination of skin excision biopsies remains the standard method for melanoma diagnosis and prognosis. Significant morphological overlap between benign and malignant lesions complicates diagnosis, and tumour thickness is not always an accurate predictor of prognosis.

METHODS:

To identify improved molecular markers to support histological examination, we used microarray analysis of formalin-fixed and paraffin-embedded samples from different stages of melanomagenesis to identify differentially expressed microRNAs (miRNAs). Differential expression was validated by qRT-PCR, and functional studies were carried out after transfection of miRNA precursors or inhibitors into melanoma cells to modulate miRNA expression.

RESULTS:

In all, 20 miRNAs showed highly significant differential expression between benign naevi and either primary or metastatic melanomas, the majority being downregulated in melanoma, whereas only 2 miRNAs, namely miR-203 and miR-205, were differentially expressed between primary and metastatic melanomas. In functional in vitro assays, overexpression of miR-200c and miR-205 inhibited anchorage-independent colony formation and overexpression of miR-211 inhibited both anchorage-independent colony formation and invasion.

CONCLUSION:

We have identified a series of differentially expressed miRNAs that could be useful as diagnostic or prognostic markers for melanoma and have shown that three miRNAs (namely miR-200c, miR-205 and miR-211) act as tumour suppressors.