Ventura Andrea, Young Amanda G, Winslow Monte M, Lintault Laura, Meissner Alex, Erkeland Stefan J, Newman Jamie, Bronson Roderick T, Crowley Denise, Stone James R, Jaenisch Rudolf, Sharp Phillip A, Jacks Tyler
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell. 2008 Mar 7;132(5):875-86. doi: 10.1016/j.cell.2008.02.019.
miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-1792 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR-17 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 approximately 92 cluster is also essential for B cell development. Absence of miR-17 approximately 92 leads to increased levels of the proapoptotic protein Bim and inhibits B cell development at the pro-B to pre-B transition. Furthermore, while ablation of miR-106b approximately 25 or miR-106a approximately 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b approximately 25 and miR-17 approximately 92 die at midgestation. These results provide key insights into the physiologic functions of this family of microRNAs and suggest a link between the oncogenic properties of miR-17 approximately 92 and its functions during B lymphopoiesis and lung development.
miR - 1792、miR - 106b25和miR - 106a363属于高度保守的miRNA簇家族。在人类癌症中观察到miR - 1792的扩增和过表达，并且其致癌特性已在B细胞淋巴瘤小鼠模型中得到证实。在此我们表明，缺乏miR - 1792的小鼠出生后不久因肺发育不全和室间隔缺损而死亡。miR - 1792簇对于B细胞发育也至关重要。缺乏miR - 1792会导致促凋亡蛋白Bim水平升高，并在B前体细胞向pre - B细胞转变阶段抑制B细胞发育。此外，虽然缺失miR - 106b25或miR - 106a363没有明显的表型后果，但同时缺乏miR - 106b25和miR - 1792的复合突变胚胎在妊娠中期死亡。这些结果为该miRNA家族的生理功能提供了关键见解，并表明miR - 1792的致癌特性与其在B淋巴细胞生成和肺发育过程中的功能之间存在联系。
