Mir-106b通过PTEN/AKT/FOXO3通路调控胶质瘤干细胞分化的机制研究

Mir-106b can promotes carcinogenicity in many known human cancers.Our preliminary study found that mir-106b,which is up-regulated in glioma ,could promote cell proliferation while inhibit cell apoptosis in vitro and in vivo via PTEN/AKT signal pathway.FOXO3 is a important downstream gene of PTEN/AKT pathway.Some data show that FOXO3 can promote differentiation of glioma stem cells,but the regulatory mechanism is unknown.Induction of glioma stem cells differentiation can efficiently enhance sensibility to chemotherapy,which could be an important method to treat high-grade glioma.FOXO3 can also inhibit expression of mir-10b.We speculate that mir-106b may regulate expression of FOXO3 via PTEN/AKT pathway to be mir-106b-FOXO3 loop,which can inhibit glioma stem cells differentiation and then downregulate sensibility to chemotherapy of glioma.We will study with antisense nucleotide transfection,plasmid transfection,siRNA interference ,nude mice models and some other methods,to explore the role of mir-106b in glioma stem cells differentiation in vitro and in vivo.The results may provide some more effective targets for the treatment of high-grade glioma.

Mir-106b在多种人体恶性肿瘤中起促癌作用。我们的前期研究发现，mir-106b在胶质瘤中高表达，可通过PTEN/AKT通路在体内外促进胶质瘤细胞的增殖，抑制凋亡。FOXO3是PTEN/AKT通路的重要下游基因。有资料显示，FOXO3可促进胶质瘤干细胞的分化，但其上游调控机制不详。诱导胶质瘤干细胞分化能提高胶质瘤对化疗的敏感性，可成为治疗高级别胶质瘤的重要手段。FOXO3还可抑制mir-106b的表达。我们推测mir-106b可能通过PTEN/AKT通路调控FOXO3的表达，形成mir-106b-FOXO3环路，抑制胶质瘤干细胞的分化。本课题拟应用反义寡核苷酸转染、质粒转染、siRNA干扰、胶质瘤原位种植裸鼠模型等技术和方法，以揭示mir-106b在体内外对胶质瘤干细胞分化的调控作用，进而为高级别胶质瘤提供新的更有效的治疗靶点。