HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells

1997 ◽  
Vol 33 (12) ◽  
pp. 2071-2074 ◽  
Author(s):  
R.A Ross ◽  
D.L Lazarova ◽  
G.T Manley ◽  
P.S Smitt ◽  
B.A Spengler ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Mycn Expression

scholarly journals HuB and HuD repress telomerase activity by dissociating HuR from TERC

2021 ◽  
Author(s):  
Xiaolei Cheng ◽  
Xiaoping Gu ◽  
Tianjiao Xia ◽  
Zhengliang Ma ◽  
Zhongzhou Yang ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Neuroblastoma Cells ◽  
Telomerase Activity ◽  
Core Complex ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Specific Proteins

Abstract The ubiquitous RNA-binding protein HuR (ELAVL1) promotes telomerase activity by associating with the telomerase noncoding RNA TERC. However, the role of the neural-specific members HuB, HuC, and HuD (ELAVL2–4) in telomerase activity is unknown. Here, we report that HuB and HuD, but not HuC, repress telomerase activity in human neuroblastoma cells. By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT–TERC core complex. Furthermore, HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previously shown to enhance telomerase activity to promote cell growth. Our findings reveal a novel mechanism controlling telomerase activity in human neuroblastoma cells that involves a competition between HuR and the related, neural-specific proteins HuB and HuD.

Expression and Down-Regulation by Retinoic Acid of IGF Binding Protein-2 and -4 in Medium from Human Neuroblastoma Cells

1994 ◽  
Vol 6 (4) ◽  
pp. 409-413 ◽  
Author(s):  
Sergio Bernardini ◽  
Stefano Cianfarani ◽  
Anna Spagnoli ◽  
Margherita Annicchiarico-Petruzzelli ◽  
Gerry Melino ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Binding Protein ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Down Regulation ◽  
Human Neuroblastoma ◽  
Igf Binding ◽  
Igf Binding Protein

scholarly journals RNA binding protein HuD promotes autophagy and tumor stress survival by suppressing mTORC1 activity and augmenting ARL6IP1 levels

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Kausik Bishayee ◽  
Khadija Habib ◽  
Uddin Md. Nazim ◽  
Jieun Kang ◽  
Aniko Szabo ◽  
...  
Keyword(s):  
Cancer Survival ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Neuroblastoma Cells ◽  
Cancer Type ◽  
Rna Targets ◽  
Stress Survival ◽  
Promote Cell Survival ◽  
Rna Immunoprecipitation

Abstract Background Neuronal-origin HuD (ELAVL4) is an RNA binding protein overexpressed in neuroblastoma (NB) and certain other cancers. The RNA targets of this RNA binding protein in neuroblastoma cells and their role in promoting cancer survival have been unexplored. In the study of modulators of mTORC1 activity under the conditions of optimal cell growth and starvation, the role of HuD and its two substrates were studied. Methods RNA immunoprecipitation/sequencing (RIP-SEQ) coupled with quantitative real-time PCR were used to identify substrates of HuD in NB cells. Validation of the two RNA targets of HuD was via reverse capture of HuD by synthetic RNA oligoes from cell lysates and binding of RNA to recombinant forms of HuD in the cell and outside of the cell. Further analysis was via RNA transcriptome analysis of HuD silencing in the test cells. Results In response to stress, HuD was found to dampen mTORC1 activity and allow the cell to upregulate its autophagy levels by suppressing mTORC1 activity. Among mRNA substrates regulated cell-wide by HuD, GRB-10 and ARL6IP1 were found to carry out critical functions for survival of the cells under stress. GRB-10 was involved in blocking mTORC1 activity by disrupting Raptor-mTOR kinase interaction. Reduced mTORC1 activity allowed lifting of autophagy levels in the cells required for increased survival. In addition, ARL6IP1, an apoptotic regulator in the ER membrane, was found to promote cell survival by negative regulation of apoptosis. As a therapeutic target, knockdown of HuD in two xenograft models of NB led to a block in tumor growth, confirming its importance for viability of the tumor cells. Cell-wide RNA messages of these two HuD substrates and HuD and mTORC1 marker of activity significantly correlated in NB patient populations and in mouse xenografts. Conclusions HuD is seen as a novel means of promoting stress survival in this cancer type by downregulating mTORC1 activity and negatively regulating apoptosis.

ZAR1 knockdown promotes the differentiation of human neuroblastoma cells by suppression of MYCN expression

2017 ◽  
Vol 34 (9) ◽  
Author(s):  
Yosuke Watanabe ◽  
Yoshiaki Ishizuka ◽  
Takayuki Hirano ◽  
Eri Nagasaki-Maeoka ◽  
Reina Hoshi ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Mycn Expression
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