BACKGROUND The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells. METHODS Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed. RESULTS We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells. CONCLUSIONS It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

中文翻译：

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长非编码 RNA HULC 通过自噬通过 miR675-PKM2 途径上调 CyclinD1，从而加速人肝癌干细胞的生长。


背景技术 HULC 的功能已在多种癌症中得到证实。然而，其在人类肝癌干细胞中的作用机制尚未阐明。方法从Huh7细胞中分离肝癌干细胞；进行体内外基因感染和肿瘤发生试验。结果我们证明 HULC 在体外和体内促进肝癌干细胞的生长。从机制上讲，HULC 依赖 miR675 增强 Sirt1 的表达，然后通过 Sirt1 诱导细胞自噬。 HULC 在人肝癌干细胞中增强 CyclinD1，从而增加 pRB，并通过自噬-miR675-PKM2 途径抑制 P21 WAF1/CIP 1。最终，我们的结果表明 CyclinD1 是肝癌干细胞中 HULC 的致癌功能所必需的。结论揭示了HULC的关键分子信号通路，为基于HULC寻找有效的肿瘤治疗靶点提供了重要的基础信息。