造血干细胞（HSCs）靠糖酵解而白血病干细胞（LSCs）依赖氧化磷酸化（OXPHOS）供能，但转换机制不清。我们曾报道miR-31-5p表达在实体瘤细胞增强Warburg Effect。目前我们发现miR-31-5p在HSCs表达但在LSCs中丢失并改变HSCs的能量代谢模式。我们推测：HSCs中miR-31-5p丢失导致其靶基因FIH表达增强，抑制了HIF-1信号并导致丙酮酸脱氢酶激活，丙酮酸因此进入线粒体，启动了OXPHOS；同时，这种代谢改变可能成为诱导HSCs恶性转化的关键因素，从而参与了LSCs的形成及白血病的发生发展。本项目结合临床样本分析，详细研究miR-31-5p体内外对HSCs生物学行为的调控。结果将提供能量代谢模式改变在HSCs恶性转化中的关键证据，以及LSCs的可能来源和白血病形成起始因素的关键线索。

Hematopoietic stem cells（HSCs）use anaerobic glycolysis to produce ATP, whereas leukemia stem cells（LSCs）obtain ATP mainly from oxidative phosphorylation (OXPHOS). But the underlining mechanism is unclear. We previously revealed that miR-31-5p is expressed in solid tumor cells enhance Warburg effect. We here find that miR-31-5p is expressed in HSCs, whereas is lost in LSCs, further alternating energy metabolic modes of HSCs. Thus, we speculate that loss of miR-31-5p leads to the enhanced expression of FIH, the target of miR-31-5p, the inhibition of HIF-1 signaling, and the activation of PDH. Therefore pyruvate enters to mitochondrion and initiates OXPHOS. Meanwhile, the alternation of metabolic modes is likely to be a key factor in malignant transformation of HSCs, further involving the formation of LSCs and the development of leukemia. In this study, combined with clinical sample, analysis we will detailedly investigate the regulatory role of miR-31-5p on biological behavior of HSCs in vitro and in vivo. The findings will provide key evidence for the alternation of energy metabolic modes on HSCs malignant transformation, and key clues to the possible origin of LSCs and the initial course of leukemia.