Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy

Abstract

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.