A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)

作者：Mavrakis Konstantinos J; Van der Meulen Joni; Wolfe Andrew L; Liu Xiaoping; Mets Evelien; Taghon Tom; Khan Aly A; Setti Manu; Rondou Pieter; Vandenberghe Peter; Delabesse Eric; Benoit Yves; Socci Nicholas B; Leslie Christina S; Van Vlierberghe Pieter; Speleman Frank; Wendel Hans Guido^*

来源：Nature Genetics, 2011, 43(7): 673-U89.

DOI：10.1038/ng.858

The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer.

• 出版日期2011-7