AUTHOR=Marção Maycon , Müller Susanne , Xavier Pedro Luiz P. , Malta Tathiane M. 

TITLE=Stemness inhibition by (+)-JQ1 in canine and human mammary cancer cells revealed by machine learning

JOURNAL=Frontiers in Drug Discovery

VOLUME=Volume 2 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2022.953988

DOI=10.3389/fddsv.2022.953988

ISSN=2674-0338

ABSTRACT=Stemness is a phenotype associated with cancer initiation and progression, malignancy, and therapeutic resistance, exhibiting particular molecular signatures. Targeting stemness has been proposed as a promising strategy against breast cancer stem cells that can play a key role in breast cancer progression, metastasis, and multiple drug resistance. Here, using a one-class logistic regression machine learning algorithm (OCLR), we provide the stemness index (mRNAsi) of different canine non-tumor somatic and pluripotent stem cells and canine mammary cancer cells. We confirm that inhibition of BET proteins by (+)-JQ1 reduces stemness in a high mRNAsi canine cancer cell. Furthermore, using public data, we observed that (+)-JQ1 can also decrease stemness in human triple-negative breast cancer cells. Our work suggests that mRNAsi can be used to estimate stemness in different species and confirm epigenetic modulation by BET inhibition as a promising strategy for modulating the stemness phenotype in canine and human mammary cancer cells.