期刊
STEM CELL RESEARCH & THERAPY
卷 11, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-019-1528-y
关键词
HULC; CyclinD1; miR675; PKM2; Autophagy
资金
- National Natural Science Foundation of China [81773158]
- Science and Technology Commission of Shanghai Municipality Basic Research Field Project [19JC1415200]
BackgroundThe functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells.MethodsLiver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed.ResultsWe 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.ConclusionsIt reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.
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