MicroRNAs and gene regulation in breast cancer

2020 ◽  
Vol 34 (11) ◽  
Author(s):  
Fatma Abdalla ◽  
Bhupendra Singh ◽  
Hari K. Bhat
2019 ◽  
Vol 19 (2) ◽  
pp. 245-260 ◽  
Author(s):  
Elena Alexandrova ◽  
Giorgio Giurato ◽  
Pasquale Saggese ◽  
Giovanni Pecoraro ◽  
Jessica Lamberti ◽  
...  

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.


PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0225180 ◽  
Author(s):  
Aisling M. Redmond ◽  
Soleilmane Omarjee ◽  
Igor Chernukhin ◽  
Muriel Le Romancer ◽  
Jason S. Carroll

2016 ◽  
Vol 1859 (11) ◽  
pp. 1389-1397 ◽  
Author(s):  
A. Rasim Barutcu ◽  
Deli Hong ◽  
Bryan R. Lajoie ◽  
Rachel Patton McCord ◽  
Andre J. van Wijnen ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Keturah Crease ◽  
Colby Williams ◽  
Peng ma ◽  
Elena Skripnikova ◽  
Thomas Wiese

Entropy ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 195 ◽  
Author(s):  
Guillermo de Anda-Jáuregui ◽  
Jesús Espinal-Enriquez ◽  
Enrique Hernández-Lemus

Gene regulation may be studied from an information-theoretic perspective. Gene regulatory programs are representations of the complete regulatory phenomenon associated to each biological state. In diseases such as cancer, these programs exhibit major alterations, which have been associated with the spatial organization of the genome into chromosomes. In this work, we analyze intrachromosomal, or cis-, and interchromosomal, or trans-gene regulatory programs in order to assess the differences that arise in the context of breast cancer. We find that using information theoretic approaches, it is possible to differentiate cis-and trans-regulatory programs in terms of the changes that they exhibit in the breast cancer context, indicating that in breast cancer there is a loss of trans-regulation. Finally, we use these programs to reconstruct a possible spatial relationship between chromosomes.


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