scholarly journals The 3′-Untranslated Region of p21WAF1mRNA Is a Compositecis-Acting Sequence Bound by RNA-binding Proteins from Breast Cancer Cells, Including HuR and Poly(C)-binding Protein

2002 ◽  
Vol 278 (5) ◽  
pp. 2937-2946 ◽  
Author(s):  
Keith M. Giles ◽  
John M. Daly ◽  
Dianne J. Beveridge ◽  
Andrew M. Thomson ◽  
Dominic C. Voon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Untranslated Region ◽  
Breast Cancer Cells ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein

scholarly journals Identification of a Novel AU-Rich Element in the 3′ Untranslated Region of Epidermal Growth Factor Receptor mRNA That Is the Target for Regulated RNA-Binding Proteins

2001 ◽  
Vol 21 (6) ◽  
pp. 2070-2084 ◽  
Author(s):  
L. A. Balmer ◽  
D. J. Beveridge ◽  
J. A. Jazayeri ◽  
A. M. Thomson ◽  
C. E. Walker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mrna Stability ◽  
Breast Cancer Cells ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Growth Factor Receptor ◽  
Human Breast ◽  
Shift Analysis

ABSTRACT The epidermal growth factor receptor (EGF-R) plays an important role in the growth and progression of estrogen receptor-negative human breast cancers. EGF binds with high affinity to the EGF-R and activates a variety of second messenger pathways that affect cellular proliferation. However, the underlying mechanisms involved in the regulation of EGF-R expression in breast cancer cells are yet to be described. Here we show that the EGF-induced upregulation of EGF-R mRNA in two human breast cancer cell lines that overexpress EGF-R (MDA-MB-468 and BT-20) is accompanied by stabilization (>2-fold) of EGF-R mRNA. Transient transfections using a luciferase reporter identified a novel EGF-regulated ∼260-nucleotide (nt)cis-acting element in the 3′ untranslated region (3′-UTR) of EGF-R mRNA. This cis element contains two distinct AU-rich sequences (∼75 nt), EGF-R1A with two AUUUA pentamers and EGF-R2A with two AUUUUUA extended pentamers. Each independently regulated the mRNA stability of the heterologous reporter. Analysis of mutants of the EGF-R2A AU-rich sequence demonstrated a role for the 3′ extended pentamer in regulating basal turnover. RNA gel shift analysis identified cytoplasmic proteins (∼55 to 80 kDa) from breast cancer cells that bound specifically to the EGF-R1A and EGF-R2A cis-acting elements and whose binding activity was rapidly downregulated by EGF and phorbol esters. RNA gel shift analysis of EGF-R2A mutants identified a role for the 3′ extended AU pentamer, but not the 5′ extended pentamer, in binding proteins. These EGF-R mRNA-binding proteins were present in multiple human breast and prostate cancer cell lines. In summary, these data demonstrate a central role for mRNA stabilization in the control of EGF-R gene expression in breast cancer cells. EGF-R mRNA contains a novel complex AU-rich 260-nt cis-acting destabilizing element in the 3′-UTR that is bound by specific and EGF-regulatedtrans-acting factors. Furthermore, the 3′ extended AU pentamer of EGF-R2A plays a central role in regulating EGF-R mRNA stability and the binding of specific RNA-binding proteins. These findings suggest that regulated RNA-protein interactions involving this novel cis-acting element will be a major determinant of EGF-R mRNA stability.

The RNA‐binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth

2015 ◽  
Vol 30 (1) ◽  
pp. 149-159 ◽  
Author(s):  
George R. Nahas ◽  
Raghav G. Murthy ◽  
Shyam A. Patel ◽  
Teja Ganta ◽  
Steven J. Greco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals RNA-binding protein CUGBP1 controls the differential INSR splicing in molecular subtypes of breast cancer cells and affects cell aggressiveness

2019 ◽  
Vol 41 (9) ◽  
pp. 1294-1305 ◽  
Author(s):  
Gena Huang ◽  
Chen Song ◽  
Ning Wang ◽  
Tao Qin ◽  
Silei Sui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Molecular Subtypes ◽  
Binding Protein ◽  
Receptor Gene ◽  
Rna Binding Protein ◽  
Breast Cancer Cell Lines ◽  
Insulin Receptor Gene

Abstract The insulin receptor gene (INSR) undergoes alternative splicing to give rise to two functionally related, but also distinct, isoforms IR-A and IR-B, which dictate proliferative and metabolic regulations, respectively. Previous studies identified the RNA-binding protein CUGBP1 as a key regulator of INSR splicing. In this study, we show that the differential splicing of INSR occurs more frequently in breast cancer than in non-tumor breast tissues. In breast cancer cell lines, the IR-A:IR-B ratio varies in different molecular subtypes, knockdown or overexpression of CUGBP1 gene in breast cancer cells altered IR-A:IR-B ratio through modulation of IR-A expression, thereby reversed or enhanced the insulin-induced oncogenic behavior of breast cancer cells, respectively. Our data revealed the predominant mitogenic role of IR-A isoform in breast cancer and depicted a novel interplay between INSR and CUGBP1, implicating CUGBP1 and IR-A isoform as the potential therapeutic targets and biomarkers for breast cancer.

scholarly journals Feedback Regulation between Zipcode Binding Protein 1 and β-Catenin mRNAs in Breast Cancer Cells

2008 ◽  
Vol 28 (16) ◽  
pp. 4963-4974 ◽  
Author(s):  
Wei Gu ◽  
Amber L. Wells ◽  
Feng Pan ◽  
Robert H. Singer
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Translational Control ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Binding Protein ◽  
Rna Stability ◽  
Feedback Regulation

ABSTRACT ZBP1 (zipcode binding protein 1) is an RNA-binding protein involved in many posttranscriptional processes, such as RNA localization, RNA stability, and translational control. ZBP1 is abundantly expressed in embryonic development, but its expression is silenced in most adult tissues. Reactivation of the ZBP1 gene has been reported in various human tumors. In this study, we identified a detailed molecular mechanism of ZBP1 transactivation in breast cancer cells. We show that β-catenin, a protein that functions in both cell adhesion and transcription, specifically binds to the ZBP1 promoter via a conserved β-catenin/TCF4 response element and activates its gene expression. ZBP1 activation is also closely correlated with nuclear translocation of β-catenin in human breast tumors. We further demonstrate feedback regulation by finding that ZBP1 physically associates with β-catenin mRNA in vivo and increases its stability. These experiments suggest that in breast cancer cells, the expression of ZBP1 and the expression of β-catenin are coordinately regulated. β-Catenin mediates the transcription of the ZBP1 gene, while ZBP1 promotes the stability of β-catenin mRNA.

Identification of RNA-binding proteins specific to Xenopus Eg maternal mRNAs: association with the portion of Eg2 mRNA that promotes deadenylation in embryos

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 1193-1202
Author(s):  
V. Legagneux ◽  
P. Bouvet ◽  
F. Omilli ◽  
S. Chevalier ◽  
H.B. Osborne
Keyword(s):  
Untranslated Region ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Untranslated Regions ◽  
Cytoplasmic Polyadenylation ◽  
Element Binding Protein ◽  
Maternal Mrnas ◽  
Post Transcriptional Regulation

Maternal Xenopus Eg mRNAs have been previously identified as transcripts that are specifically deadenylated after fertilization and degraded after the mid blastula transition. Destabilizing cis sequences were previously localised in the 3′ untranslated region of Eg2 mRNA. In order to characterize possible trans-acting factors which are involved in the post-transcriptional regulation of Eg mRNAs, gel-shift and u.v. cross-linking experiments were performed, which allowed the identification of a p53-p55 RNA-binding protein doublet specific for the 3′ untranslated regions of Eg mRNAs. These p53-p55 proteins do not bind to the 3′ untranslated regions of either ornithine decarboxylase or phosphatase 2Ac mRNAs, which remain polyadenylated in embryos. These novel RNA-binding proteins are distinct from the cytoplasmic polyadenylation element-binding protein that controls the polyadenylation of maternal mRNAs in maturing Xenopus oocytes, and from previously identified thermoresistant RNA-binding proteins present in oocyte mRNP storage particles. The p53-p55 bind a portion of the Eg2 mRNA 3′ untranslated region, distinct from the previously identified destabilizing region, that is able to confer the postfertilization deadenylation of CAT-coding chimeric mRNAs. This suggests that the p53-p55 RNA-binding proteins are good candidates for trans-acting factors involved in the deadenylation of Eg mRNAs in Xenopus embryos.

scholarly journals Identification of a Three-RNA Binding Proteins (RBPs) Signature Predicting Prognosis for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Hefen Sun ◽  
Xuan Li ◽  
Qiqi Liu ◽  
Yuanyuan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Prognostic Model ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cellular Viability ◽  
Normal Tissues ◽  
Cox Analysis

BackgroundTo date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.MethodsBased on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan–Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments in vitro, and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.ResultsHere, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells in vitro. Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer via targeting MRPL12, MRPL13 and POP1 simultaneously.ConclusionThis study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.

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