生物谷Bioon.com 訊 加拿大女王大學(xué)的研究人員識(shí)別了黑素瘤誘導(dǎo)相關(guān)的miRNAs的差異表達(dá)。這項(xiàng)研究是由Victor Tron博士負(fù)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(xì)胞的惡性腫瘤,相對(duì)較罕見(jiàn),,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(dá),,但其在癌癥發(fā)展中具有重要作用,。
為了證實(shí)"miRNAs的差異表達(dá)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(dá)水平,。在檢測(cè)過(guò)程中,,他們一共發(fā)現(xiàn)了31個(gè)表達(dá)差異,其中的一個(gè)是miR-193b,,其在所有檢測(cè)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(dá)能抑制增殖,,同時(shí)也能夠下調(diào)很多基因,,其中包括一種調(diào)控細(xì)胞分裂的基因。檢測(cè)結(jié)果表明,,miR-193b調(diào)節(jié)異??赡軐?dǎo)致黑素瘤的發(fā)生。
研究人員表示,,接下來(lái)他們將對(duì)miR-193b做進(jìn)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?yàn)樵诤谒亓黾?xì)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)
編輯推薦更多閱讀
PNAS:改造信號(hào)蛋白可阻止黑素瘤細(xì)胞轉(zhuǎn)移
Nature:與黑素瘤相關(guān)的基因突變
Nature:人類惡性黑素瘤干細(xì)胞
Cell:microRNA對(duì)基因表達(dá)轉(zhuǎn)錄調(diào)控
Cancer Research:microRNA-155促進(jìn)腫瘤發(fā)生 或?yàn)槁?lián)系炎癥和癌癥橋梁
Nature Cell Biology:microRNA分子miR-151與肝癌轉(zhuǎn)移
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.