Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Nucleic Acids Res. 2018 Aug 21;46(14):7108-7123. doi: 10.1093/nar/gky484.
The miR-34 family of microRNAs suppresses the expression of proteins involved in pluripotency and oncogenesis. miR-34 expression is frequently reduced in cancers; however, the regulation of their expression is not well understood. We used genome-wide miRNA profiling and mechanistic analysis to show that SUMOylation regulates miR-34b/c expression, which impacts the expression of c-Myc and other tested miR-34 targets. We used site-directed mutagenesis and other methods to show that protein kinase B (also known as Akt) phosphorylation of FOXO3a plays an important role in SUMOylation-dependent expression of miR-34b/c. This study reveals how the miR-34-targeted gene expression program is regulated by SUMOylation and shows that SUMOylation need not regulate target proteins through direct modification, but instead can act through the expression of their targeting miRNAs.
miR-34 微 RNA 家族抑制多能性和致癌基因相关蛋白的表达。miR-34 的表达在癌症中经常减少；然而，它们的表达调控还不是很清楚。我们使用全基因组 miRNA 分析和机制分析表明，SUMO 化调节 miR-34b/c 的表达，这会影响 c-Myc 和其他测试的 miR-34 靶基因的表达。我们使用定点突变和其他方法表明，蛋白激酶 B（也称为 Akt）对 FOXO3a 的磷酸化在 SUMO 化依赖的 miR-34b/c 表达中起着重要作用。这项研究揭示了 miR-34 靶向基因表达程序如何被 SUMO 化调控，并表明 SUMO 化不必通过直接修饰来调节靶蛋白，而是可以通过表达它们的靶向 miRNA 来发挥作用。
