近日，中国科技大学吴缅教授研究组与澳大利亚纽卡斯尔大学张旭东教授合作，发现一种微小RNA149*分子参与了黑色素肿瘤的发生和发展，并揭示该小分子促进黑色素瘤发生的新机制。相关研究成果近期发表在国际著名学术期刊《美国科学院院刊》（PNAS）上。这项研究成果，有望给黑色素瘤的诊断和治疗带来新的希望。
黑色素瘤俗称皮肤癌，是一种危害性很大、发病率很高的恶性肿瘤。吴缅等研究人员通过对60位黑色素瘤临床病人的病例样本的分析研究，证实了RNA149*分子的含量较健康人正常组织呈显著上升，这意味着该小分子可以作为黑色素瘤临床诊断的依据。另外，小鼠实验表明，降低该小分子含量可以明显抑制黑色素瘤的生长，这为治疗黑色素瘤提供了一个潜在靶位，用于临床药物的研发。专家称，这一研究成果将有可能用于改善黑色素瘤的诊断和治疗。（生物谷Bioon.com）
doi:10.1073/pnas.1019312108
PMC:
PMID:
MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma
Lei Jin, Wang Lai Hu, Chen Chen Jiang, Jia Xu Wang, Chuan Chun Han, Ping Chu, Lin Jie Zhang, Rick F. Thorne, James Wilmott, Richard A. Scolyer, Peter Hersey, Xu Dong Zhang, and Mian Wu
The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation by activation of the DNA repair machinery to preserve the cell, or by induction of apoptosis to eliminate the cell should the damage prove irrevocable. The gene encoding p53 frequently undergoes inactivating mutations in many human cancers, but WT p53 is often expressed at high levels in melanoma, which, as judged from the malignant nature of the disease, fails to act as an effective tumor suppressor. Here we show that p53 directly up-regulates microRNA-149* (miR-149*) that in turn targets glycogen synthase kinase-3α, resulting in increased expression of Mcl-1 and resistance to apoptosis in melanoma cells. Although deficiency in miR-149* undermined survival of melanoma cells and inhibited melanoma growth in a mouse xenograft model, elevated expression of miR-149* was found in fresh human metastatic melanoma isolates, which was associated with decreased glycogen synthase kinase-3α and increased Mcl-1. These results reveal a p53-dependent, miR-149*–mediated pathway that contributes to survival of melanoma cells, provides a rational explanation for the ineffectiveness of p53 to suppress melanoma, and identifies the expression of miR-149* as a mechanism involved in the increased expression of Mcl-1 in melanoma cells.
