The role of microRNAs during the genesis of medulloblastomas induced by the hedgehog pathway  

作　　者：Steven Y Cheng 

机构地区：[1]Department of Developmental Genetics and Center for Regenerative Medicine,Nanjing Medical University

出　　处：《The Journal of Biomedical Research》2011年第1期42-48,共7页生物医学研究杂志（英文版）

摘　　要：Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.

关 键 词：Hedgehog signaling pathway MICRORNAS miR-154 cluster MEDULLOBLASTOMAS 

分 类 号：R739.4[医药卫生—肿瘤]