例如:"lncRNA", "apoptosis", "WRKY"

RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma.

Cancer Discov. 2014 Apr;4(4):434-51. Epub 2014 Jan 27
Zhi Xiong Chen 1 , Karin Wallis , Stuart M Fell , Veronica R Sobrado , Marie C Hemmer , Daniel Ramsköld , Ulf Hellman , Rickard Sandberg , Rajappa S Kenchappa , Tommy Martinson , John I Johnsen , Per Kogner , Susanne Schlisio
Zhi Xiong Chen 1 , Karin Wallis , Stuart M Fell , Veronica R Sobrado , Marie C Hemmer , Daniel Ramsköld , Ulf Hellman , Rickard Sandberg , Rajappa S Kenchappa , Tommy Martinson , John I Johnsen , Per Kogner , Susanne Schlisio
+ et al

[No authors listed]

Author information
  • 1 1Ludwig Institute for Cancer Research Ltd.; 2Department of Cell and Molecular Biology, Karolinska Institutet; 3Department of Women's and Children's Health, Karolinska University Hospital, Stockholm; 4Ludwig Institute for Cancer Research Ltd., Biomedical Center, Uppsala; 5Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden; and 6Moffitt Cancer Center, Neuro-Oncology Program, Tampa, Florida.

摘要


UNLABELLED:Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis. SIGNIFICANCE:KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation.

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
cell lineplasmidshRNAsource name
NB1 shDHX9 KIF1Bbeta biol repl C
Homo sapiens GSM1087268: NB1 shDHX9 KIF1Bbeta biol repl C; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 NB1 KIF1Bbeta(600-1400) DHX9 NB1 cell line
NB1 shDHX9 KIF1Bbeta biol repl B
Homo sapiens GSM1087267: NB1 shDHX9 KIF1Bbeta biol repl B; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 NB1 KIF1Bbeta(600-1400) DHX9 NB1 cell line
NB1 shDHX9 KIF1Bbeta biol repl A
Homo sapiens GSM1087266: NB1 shDHX9 KIF1Bbeta biol repl A; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 NB1 KIF1Bbeta(600-1400) DHX9 NB1 cell line
NB1 shDHX9 controlplasmid biol repl C
Homo sapiens GSM1087265: NB1 shDHX9 controlplasmid biol repl C; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 NB1 empty pcDNA3.1 vector DHX9 NB1 cell line
NB1 shDHX9 controlplasmid biol repl B
Homo sapiens GSM1087264: NB1 shDHX9 controlplasmid biol repl B; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 NB1 empty pcDNA3.1 vector DHX9 NB1 cell line