MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.

中文翻译：

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miR24-2 通过表观遗传学增强酪氨酸激酶 Src 促进人肝癌干细胞的恶性进展。


MicroRNA24-2 (miR24-2) 与人类肿瘤发生有关；然而，对其分子机制知之甚少。在此，我们的研究结果表明，miR24-2 促进人肝癌干细胞（hLCSC）的体外增殖能力和体内致瘤能力。从机械角度来看，miR24-2 靶向蛋白精氨酸甲基转移酶 7 (PRMT7) 的 3' UTR (2,627-2,648)，抑制 prmt7 基因的翻译能力。此外，miR24-2通过减少PRMT7抑制组蛋白H4精氨酸3的二甲基化/三甲基化，然后通过长非编码RNA HULC促进Nanog的表达。值得注意的是，miR24-2 通过 miR675 抑制组蛋白脱乙酰酶 HDAC3，从而促进组蛋白 H4 在赖氨酸 16 处的乙酰化。随后，miR24-2 增强 LC3 和 ATG4 之间依赖 PI3K 的相互作用，并触发细胞自噬。引人注目的是，miR24-2 在 hLCSC 中通过自噬体-P62 抑制丙酮酸激酶 M1 的降解。此外，miR24-2 通过促进 PKM1 与 hLCSC 中 Src 启动子区域的结合来增强 Src 的活性。特别是，我们的结果还表明 src 基因决定 miR24-2 的致癌功能。这些结果为基于miR24-2的肝癌治疗靶点和诊断标志物的发现提供了有价值的理论依据。