惡性黑色素瘤的發(fā)病率正在逐年上升，并且其上升速度比任何其他癌癥都要快,。皮膚切除活檢仍然是黑色素瘤診斷和預(yù)后判斷的標(biāo)準(zhǔn)方法,。良性和惡性病變組織之間有顯著的形態(tài)重疊，腫瘤的厚度并不總是一個(gè)準(zhǔn)確的預(yù)測指標(biāo),。
因此確定新的分子標(biāo)記物以支持組織學(xué)檢查非常有必要,，近日研究人員對不同病理階段的福爾馬林固定、石蠟包埋的樣本進(jìn)行微陳列分析,，以便識別差異表達(dá)的微小RNA（miRNA）,。相關(guān)研究論文發(fā)表在British Journal of Cancer雜志上。
采用QRT-PCR驗(yàn)證這些微小RNA的差異表達(dá),，miRNA的功能學(xué)研究采用黑色素瘤細(xì)胞轉(zhuǎn)染能調(diào)節(jié)miRNA表達(dá)的miRNA前體或抑制劑來開展,。結(jié)果發(fā)現(xiàn)有20個(gè)miRNA在良性痣和原發(fā)性或轉(zhuǎn)移性黑色瘤中存在顯著差異性表達(dá)，而其中大部分在黑色素瘤中是下調(diào)的,，而只有2個(gè)miRNA即miR-203和miR-205在原發(fā)性和轉(zhuǎn)移性黑色素瘤中是差異表達(dá)的,。
在體外試驗(yàn)中，抑制過度的miR-200C和miR-205能顯著抑制黑色素瘤細(xì)胞的克隆集落形成能力,，抑制過表達(dá)miR-211既能集落形成能力,，也能抑制黑色素瘤細(xì)胞的侵襲。該研究所確定的一系列miRNA差異表達(dá)可能用于黑色素瘤的診斷或預(yù)后指標(biāo),，其中3個(gè)miRNAs（即miR-200c,、miR-205和miR-211）發(fā)揮腫瘤抑制基因的功能。（生物谷：Bioon.com）
doi:10.1038/bjc.2011.568
PMC:
PMID:
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.
