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Abstract：
The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells.
Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed.
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.
It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.
Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed.
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.
It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.
摘要：
HULC的功能已在几种癌症中得到证实。然而,其机制尚未在人类肝癌干细胞中阐明。
从Huh7细胞中分离肝癌干细胞;进行体外和体内基因感染和肿瘤发生测试。
我们证明HULC在体外和体内促进肝癌干细胞的生长。机械上,HULC依赖于miR675增强Sirt1的表达，然后通过Sirt1诱导细胞自噬。HULC通过自噬-miR675-PKM2途径增强CyclinD1，从而增加pRB并抑制人肝癌干细胞中的P21WAF1/CIP1。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。
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。
从Huh7细胞中分离肝癌干细胞;进行体外和体内基因感染和肿瘤发生测试。
我们证明HULC在体外和体内促进肝癌干细胞的生长。机械上,HULC依赖于miR675增强Sirt1的表达，然后通过Sirt1诱导细胞自噬。HULC通过自噬-miR675-PKM2途径增强CyclinD1，从而增加pRB并抑制人肝癌干细胞中的P21WAF1/CIP1。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。
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。
