scholarly journals Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Sakari Vanharanta ◽  
Christina B Marney ◽  
Weiping Shu ◽  
Manuel Valiente ◽  
Yilong Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wnt Signaling Pathway ◽  
Experimental Models ◽  
Breast Cancer Progression ◽  
Binding Motif ◽  
Clinical Breast

The mechanisms through which cancer cells lock in altered transcriptional programs in support of metastasis remain largely unknown. Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of breast cancer progression and metastasis. RBM47 inhibited breast cancer re-initiation and growth in experimental models. Transcriptome-wide HITS-CLIP analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns and 3′UTRs. RBM47 altered splicing and abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1, inhibit tumor progression downstream of RBM47. Our work identifies RBM47 as an RNA-binding protein that can suppress breast cancer progression and demonstrates how the inactivation of a broadly targeted RNA chaperone enables selection of a pro-metastatic state.

scholarly journals E2F1 and epigenetic modifiers orchestrate breast cancer progression by regulating oxygen-dependent ESRP1 expression

Oncogenesis ◽  
2021 ◽  
Vol 10 (8) ◽  
Author(s):  
Cheemala Ashok ◽  
Neha Ahuja ◽  
Subhashis Natua ◽  
Jharna Mishra ◽  
Atul Samaiya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Breast Cancer Progression ◽  
Regulatory Mechanisms ◽  
Binding Motif ◽  
Primary Tumors ◽  
Mesenchymal Transition

AbstractEpithelial splicing regulatory protein 1 (ESRP1) is an RNA binding protein that governs the alternative splicing events related to epithelial phenotypes. ESRP1 contributes significantly at different stages of cancer progression. ESRP1 expression is substantially elevated in carcinoma in situ compared to the normal epithelium, whereas it is drastically ablated in cancer cells within hypoxic niches, which promotes epithelial to mesenchymal transition (EMT). Although a considerable body of research sought to understand the EMT-associated ESRP1 downregulation, the regulatory mechanisms underlying ESRP1 upregulation in primary tumors remained largely uncharted. This study seeks to unveil the regulatory mechanisms that spatiotemporally fine-tune the ESRP1 expression during breast carcinogenesis. Our results reveal that an elevated expression of transcription factor E2F1 and increased CpG hydroxymethylation of the E2F1 binding motif conjointly induce ESRP1 expression in breast carcinoma. However, E2F1 fails to upregulate ESRP1 despite its abundance in oxygen-deprived breast cancer cells. Mechanistically, impelled by the hypoxia-driven reduction of tet methylcytosine dioxygenase 3 (TET3) activity, CpG sites across the E2F1 binding motif lose the hydroxymethylation marks while gaining the de novo methyltransferase-elicited methylation marks. These two oxygen-sensitive epigenetic events work in concert to repel E2F1 from the ESRP1 promoter, thereby diminishing ESRP1 expression under hypoxia. Furthermore, E2F1 skews the cancer spliceome by upregulating splicing factor SRSF7 in hypoxic breast cancer cells. Our findings provide previously unreported mechanistic insights into the plastic nature of ESRP1 expression and insinuate important implications in therapeutics targeting breast cancer progression.

scholarly journals The RNA-Binding Protein Musashi-1 Regulates Proteasome Subunit Expression in Breast Cancer- and Glioma-Initiating Cells

Stem Cells ◽  
2014 ◽  
Vol 32 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Chann Lagadec ◽  
Erina Vlashi ◽  
Patricia Frohnen ◽  
Yazeed Alhiyari ◽  
Mabel Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Proteasome Subunit ◽  
Glioma Initiating Cells ◽  
Subunit Expression

scholarly journals Severe muscle wasting and denervation in mice lacking the RNA-binding protein ZFP106

2016 ◽  
Vol 113 (31) ◽  
pp. E4494-E4503 ◽  
Author(s):  
Douglas M. Anderson ◽  
Jessica Cannavino ◽  
Hui Li ◽  
Kelly M. Anderson ◽  
Benjamin R. Nelson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Motor Neurons ◽  
Knockout Mice ◽  
Muscle Wasting ◽  
Rna Binding ◽  
Neuromuscular Junctions ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Binding Motif ◽  
Nerve Muscle

Innervation of skeletal muscle by motor neurons occurs through the neuromuscular junction, a cholinergic synapse essential for normal muscle growth and function. Defects in nerve–muscle signaling cause a variety of neuromuscular disorders with features of ataxia, paralysis, skeletal muscle wasting, and degeneration. Here we show that the nuclear zinc finger protein ZFP106 is highly enriched in skeletal muscle and is required for postnatal maintenance of myofiber innervation by motor neurons. Genetic disruption of Zfp106 in mice results in progressive ataxia and hindlimb paralysis associated with motor neuron degeneration, severe muscle wasting, and premature death by 6 mo of age. We show that ZFP106 is an RNA-binding protein that associates with the core splicing factor RNA binding motif protein 39 (RBM39) and localizes to nuclear speckles adjacent to spliceosomes. Upon inhibition of pre-mRNA synthesis, ZFP106 translocates with other splicing factors to the nucleolus. Muscle and spinal cord of Zfp106 knockout mice displayed a gene expression signature of neuromuscular degeneration. Strikingly, altered splicing of the Nogo (Rtn4) gene locus in skeletal muscle of Zfp106 knockout mice resulted in ectopic expression of NOGO-A, the neurite outgrowth factor that inhibits nerve regeneration and destabilizes neuromuscular junctions. These findings reveal a central role for Zfp106 in the maintenance of nerve–muscle signaling, and highlight the involvement of aberrant RNA processing in neuromuscular disease pathogenesis.

Abstract 3271: The RNA binding protein HuR controls angiogenesis in triple negative breast cancer

2010 ◽  
Author(s):  
Ulus Atasoy ◽  
Matthew Gubin ◽  
Bob Calaluce ◽  
Wade Davis ◽  
Joseph Magee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

Abstract 2248: The Y-box-binding protein 1 is associated with breast cancer progression and metastasis

2010 ◽  
Author(s):  
Yingnan Yu ◽  
George Wai-Cheong Yip ◽  
Puay-Hoon Tan ◽  
Ken Matsumoto ◽  
Masafumi Tsujimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Binding Protein ◽  
Breast Cancer Progression
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