生物谷Bioon.com 訊 加拿大女王大學(xué)的研究人員識別了黑素瘤誘導(dǎo)相關(guān)的miRNAs的差異表達,。這項研究是由Victor Tron博士負責(zé)的,,研究結(jié)果發(fā)布在2010年5月的 American Journal of Pathology雜志上,。
黑素瘤是一種源于皮膚,粘膜,,眼和中樞神經(jīng)系統(tǒng)色素沉著區(qū)域的黑素細胞的惡性腫瘤,,相對較罕見,但是75%皮膚癌相關(guān)的死亡是由這種疾病導(dǎo)致的,。miRNAs是一類小型的遺傳分子,,并不編碼基因和調(diào)控基因表達,但其在癌癥發(fā)展中具有重要作用,。
為了證實"miRNAs的差異表達能夠?qū)е掳┌Y發(fā)生"這一猜想,,Chen等人比較了良性病變和轉(zhuǎn)移性黑素瘤中miRNAs的表達水平。在檢測過程中,,他們一共發(fā)現(xiàn)了31個表達差異,,其中的一個是miR-193b,其在所有檢測的黑素瘤組織中均顯著降低,。腫瘤組織中高水平的miR-193b表達能抑制增殖,,同時也能夠下調(diào)很多基因,其中包括一種調(diào)控細胞分裂的基因,。檢測結(jié)果表明,,miR-193b調(diào)節(jié)異常可能導(dǎo)致黑素瘤的發(fā)生,。
研究人員表示,,接下來他們將對miR-193b做進一步的研究,以理解是否miR-193b的下調(diào)作用發(fā)生在黑素瘤發(fā)展的早期。因為在黑素瘤細胞中,,miR-193b似乎具有抗增殖效果,,這或能為黑素瘤的治療提供潛在的新療法。(生物谷Bioon.com)
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Bioon.com推薦原文出處:
American Journal of Pathology DOI: 10.2353/ajpath.2010.091061
MicroRNA-193b Represses Cell Proliferation and Regulates Cyclin D1 in Melanoma
Jiamin Chen, Harriet E. Feilotter, Geneviève C. Paré, Xiao Zhang, Joshua G.W. Pemberton, Cherif Garady, Dulcie Lai, Xiaolong Yang and Victor A. Tron
Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. To better understand the role of microRNAs (miRNAs) in melanoma, the expression of 470 miRNAs was profiled in tissue samples from benign nevi and metastatic melanomas. We identified 31 miRNAs that were differentially expressed (13 up-regulated and 18 down-regulated) in metastatic melanomas relative to benign nevi. Notably, miR-193b was significantly down-regulated in the melanoma tissues examined. To understand the role of miR-193b in melanoma, functional studies were undertaken. Overexpression of miR-193b in melanoma cell lines repressed cell proliferation. Gene expression profiling identified 314 genes down-regulated by overexpression of miR-193b in Malme-3M cells. Eighteen of these down-regulated genes, including cyclin D1 (CCND1), were also identified as putative miR-193b targets by TargetScan. Overexpression of miR-193b in Malme-3M cells down-regulated CCND1 mRNA and protein by 50%. A luciferase reporter assay confirmed that miR-193b directly regulates CCND1 by binding to the 3'untranslated region of CCND1 mRNA. These studies indicate that miR-193b represses cell proliferation and regulates CCND1 expression and suggest that dysregulation of miR-193b may play an important role in melanoma development.