MicroRNAs (miRNAs) are small regulatory RNAs of relatively long half-life in non-proliferative human cells. However, in cancer cells the half-lives of miRNAs are comparatively short. To understand the mechanism of rapid miRNA turnover in cancer cells, we explored the effect of target mRNAs on the abundance of the miRNAs that repress them. We have noted an accelerated extracellular vesicle (EV)-mediated export of miRNAs in presence of their target mRNAs in mammalian cells, and this target-driven miRNA-export process is retarded by Ago2-interacting protein GW182B. The GW182 group of proteins are localized to GW182 bodies or RNA processing bodies in mammalian cells, and GW182B-dependent retardation of miRNA export depends on GW body integrity and is independent of the HuR protein-mediated auxiliary pathway of miRNA export. Our data thus support the existence of a HuR-independent pathway of miRNA export in human cells that can be targeted in MDA-MB-231 cancer cells, to increase the level of cellular let-7a, a known negative regulator of cancer growth.

中文翻译：

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GW182 蛋白限制细胞外囊泡介导的微小 RNA 在哺乳动物癌细胞中的输出

MicroRNA (miRNA) 是在非增殖性人类细胞中半衰期相对较长的小调节 RNA。然而，在癌细胞中，miRNA 的半衰期相对较短。为了了解癌细胞中 miRNA 快速更新的机制，我们探索了目标 mRNA 对抑制它们的 miRNA 丰度的影响。我们已经注意到，在哺乳动物细胞中存在靶 mRNA 的情况下，细胞外囊泡 (EV) 介导的 miRNA 加速输出，而这种靶驱动的 miRNA 输出过程被 Ago2 相互作用蛋白 GW182B 阻止。GW182 蛋白组定位于哺乳动物细胞中的 GW182 体或 RNA 加工体，GW182B 依赖的 miRNA 输出延迟取决于 GW 体的完整性，并且独立于 HuR 蛋白介导的 miRNA 输出辅助途径。