生物谷Bioon.com 讯 加拿大女王大学的研究人员识别了黑素瘤诱导相关的miRNAs的差异表达。这项研究是由Victor Tron博士负责的,研究结果发布在2010年5月的 American Journal of Pathology杂志上。
黑素瘤是一种源于皮肤,粘膜,眼和中枢神经系统色素沉着区域的黑素细胞的恶性肿瘤,相对较罕见,但是75%皮肤癌相关的死亡是由这种疾病导致的。miRNAs是一类小型的遗传分子,并不编码基因和调控基因表达,但其在癌症发展中具有重要作用。
为了证实"miRNAs的差异表达能够导致癌症发生"这一猜想,Chen等人比较了良性病变和转移性黑素瘤中miRNAs的表达水平。在检测过程中,他们一共发现了31个表达差异,其中的一个是miR-193b,其在所有检测的黑素瘤组织中均显着降低。肿瘤组织中高水平的miR-193b表达能抑制增殖,同时也能够下调很多基因,其中包括一种调控细胞分裂的基因。检测结果表明,miR-193b调节异常可能导致黑素瘤的发生。
研究人员表示,接下来他们将对miR-193b做进一步的研究,以理解是否miR-193b的下调作用发生在黑素瘤发展的早期。因为在黑素瘤细胞中,miR-193b似乎具有抗增殖效果,这或能为黑素瘤的治疗提供潜在的新疗法。(生物谷Bioon.com)
编辑推荐更多阅读
PNAS:改造信号蛋白可阻止黑素瘤细胞转移
Nature:与黑素瘤相关的基因突变
Nature:人类恶性黑素瘤干细胞
Cell:microRNA对基因表达转录调控
Cancer Research:microRNA-155促进肿瘤发生 或为联系炎症和癌症桥梁
Nature Cell Biology:microRNA分子miR-151与肝癌转移
Bioon.com推荐原文出处:
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.