scholarly journals The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer

RNA Biology ◽  
2014 ◽  
Vol 11 (6) ◽  
pp. 755-765 ◽  
Author(s):  
Jacqueline Stockley ◽  
M Eugenia M Villasevil ◽  
Colin Nixon ◽  
Imran Ahmad ◽  
Hing Y Leung ◽  
...  
2020 ◽  
Vol 117 (45) ◽  
pp. 28092-28101 ◽  
Author(s):  
Jordan E. Vellky ◽  
Sean T. McSweeney ◽  
Emily A. Ricke ◽  
William A. Ricke

Prostate cancer (CaP) driven by androgen receptor (AR) is treated with androgen deprivation; however, therapy failure results in lethal castration-resistant prostate cancer (CRPC). AR-low/negative (ARL/−) CRPC subtypes have recently been characterized and cannot be targeted by hormonal therapies, resulting in poor prognosis. RNA-binding protein (RBP)/helicase DDX3 (DEAD-box helicase 3 X-linked) is a key component of stress granules (SG) and is postulated to affect protein translation. Here, we investigated DDX3-mediated posttranscriptional regulation of AR mRNA (messenger RNA) in CRPC. Using patient samples and preclinical models, we objectively quantified DDX3 and AR expression in ARL/− CRPC. We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA immunoprecipitation, assess the effects of DDX3 gain/loss-of-function on AR expression and signaling, and address clinical implications of targeting DDX3 by assessing sensitivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo. ARL/− CRPC expressed abundant AR mRNA despite diminished levels of AR protein. DDX3 protein was highly expressed in ARL/− CRPC, where it bound to AR mRNA. Consistent with a repressive regulatory role, DDX3 localized to cytoplasmic puncta with SG marker PABP1 in CRPC. While induction of DDX3-nucleated SGs resulted in decreased AR protein expression, inhibiting DDX3 was sufficient to restore 1) AR protein expression, 2) AR signaling, and 3) sensitivity to ARSI in vitro and in vivo. Our findings implicate the RBP protein DDX3 as a mechanism of posttranscriptional regulation for AR in CRPC. Clinically, DDX3 may be targetable for sensitizing ARL/− CRPC to AR-directed therapies.


2020 ◽  
Vol 32 (18) ◽  
pp. 1357
Author(s):  
Chengcheng Xu ◽  
Dandan Ke ◽  
Liping Zou ◽  
Nianyu Li ◽  
Yingying Wang ◽  
...  

In this study, the ability of cold-induced RNA-binding protein (CIRBP) to regulate the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) in the mouse testis and mouse primary spermatocytes (GC-2spd cell line) before and after heat stress was examined to explore the molecular mechanism by which CIRBP decreases testicular injury. A mouse testicular hyperthermia model, a mouse primary spermatocyte hyperthermia model and a low CIRBP gene-expression cell model were constructed and their relevant parameters were analysed. The mRNA and protein levels of CIRBP and Sam68 were significantly decreased in the 3-h and 12-h testicular heat-stress groups, extracellular signal-regulated kinase 1/2 (ERK1/2) protein expression was not significantly affected but phospho-ERK1/2 protein levels were significantly decreased. GC-2spd cellular heat-stress results showed that the mRNA and protein concentrations of CIRBP and Sam68 were reduced 48h after heat stress. In the low CIRBP gene-expression cell model, CIRBP protein expression was significantly decreased. Sam68 mRNA expression was significantly decreased only at the maximum transfection concentration of 50nM and Sam68 protein expression was not significantly affected. These findings suggest that CIRBP may regulate the expression of Sam68 at the transcriptional level and the expression of phospho-ERK1/2 protein, both of which protect against heat-stress-induced testicular injury in mice.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruben G. de Bruin ◽  
Eric P. van der Veer ◽  
Jurriën Prins ◽  
Dae Hyun Lee ◽  
Martijn J. C. Dane ◽  
...  

1999 ◽  
pp. 61
Author(s):  
Michael E. Chen ◽  
Gail C. Fraizer ◽  
Tasneem Ahmed ◽  
Bei Zheng ◽  
Jeffrey Wilusz ◽  
...  

2020 ◽  
Author(s):  
Xiao Tan ◽  
Wen-Bin Chen ◽  
Dao-Jun Lv ◽  
Tao-Wei Yang ◽  
Kai-Hui Wu ◽  
...  

Abstract Background: The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa).Methods:SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the mRNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism.Results: We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Conclusion: Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.


2011 ◽  
Vol 286 (37) ◽  
pp. 32333-32343 ◽  
Author(s):  
Sudha Talwar ◽  
Junfei Jin ◽  
Brittany Carroll ◽  
Angen Liu ◽  
Marion Boyd Gillespie ◽  
...  

PLoS ONE ◽  
2007 ◽  
Vol 2 (10) ◽  
pp. e1107 ◽  
Author(s):  
Yanmei Huang ◽  
Ginka Genova ◽  
Mary Roberts ◽  
F. Rob Jackson

Aging ◽  
2021 ◽  
Author(s):  
Penghui Yuan ◽  
Le Ling ◽  
Xintao Gao ◽  
Taotao Sun ◽  
Jianping Miao ◽  
...  

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