新近研究表明：缺氧诱导因子2α(HIF-2α)的5'-非翻译区(5'-UTR)存在铁效应元件(IRE)，在其翻译过程中发挥重要作用。我们初步发现：HIF-2α在神经母细胞组织非缺氧区域高表达，能促进肿瘤增殖、侵袭转移及血管生成，但其蛋白表达的调控机制不明；靶向IRE的内源性微小RNA 558(hsa-miR-558)可能通过招募真核起始因子4E(eIF4E)，促进神经母细胞瘤中HIF-2α表达。本课题拟在此基础上，观测hsa-miR-558对神经母细胞瘤组织和细胞中HIF-2α表达的调控作用；观测hsa-miR-558与IRE、AGO2与eIF4E的相互作用对核糖体结合5'-UTR的影响；观测hsa-miR-558调控HIF-2α表达对神经母细胞瘤细胞体内外增殖、侵袭转移及血管生成的影响，旨在从内源性小非编码RNA角度丰富HIF-2α表达调控机理，为神经母细胞瘤的治疗提供新途径。

Recent studies indicate the existence of iron responsive element (IRE) within the 5'-untranslated region (5'-UTR) of hypoxia induced factor 2 alpha (HIF-2α), which plays an important role in its translation process. Our preliminary data show that HIF-2α is highly expressed in the non-hypoxia region of neuroblastoma tissues, and promotes the proliferation, invasion and metastasis of tumor cells. However, the mechanisms regulating its protein expression still remain largely unknown. The endogenous IRE targeting hsa-miR-558 may promote the HIF-2α expression in neuroblastoma through recurring eukaryotic translation initiation factor 4E (eIF4E). Based on these findings, this study will detect the effects of hsa-miR-558 on the expression of HIF-2α in neuroblastoma tissues and cell lines, investigate the influence of interaction between hsa-miR-558 and IRE, AGO2 and eIF4E on the binding of ribosomes with 5'-UTR, and elucidate the hsa-miR-558-induced changes in proliferation, invasion, metastasis, and angiogenesis of neuroblastoma cells in vitro and in vivo. This study will define the regulation mechanisms of HIF-2α from the insights of endogenous small non-coding RNA, and provide novel approaches for the treatment of neuroblastoma.