机器学习揭示(+)-JQ1对犬和人乳腺癌症细胞的抑制作用

Maycon Marção, S. Müller, Pedro Luiz P. Xavier, T. Malta
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引用次数: 1

摘要

遗忘是一种与癌症发生和发展、恶性肿瘤和治疗耐药性相关的表型,表现出特殊的分子特征。靶向干细胞被认为是一种很有前途的对抗癌症干细胞的策略,它可以在癌症的进展、转移和多重耐药性中发挥关键作用。在此,使用先前发表的基于多能干细胞的一类逻辑回归机器学习算法(OCLR)来预测人类癌症样本中的干性,我们提供了不同犬非肿瘤和乳腺癌症细胞的干性指数(mRNAsi)。然后,我们证实了(+)-JQ1对BET蛋白的抑制降低了高mRNAsi犬癌症细胞中的干性。此外,利用公开数据,我们观察到(+)-JQ1也可以降低人类癌症三阴性细胞的干性。我们的工作表明,mRNAsi可用于评估不同物种的干性,并证实通过BET抑制的表观遗传学调节是调节犬和人类癌症细胞干性表型的一种有前途的策略。
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Stemness inhibition by (+)-JQ1 in canine and human mammary cancer cells revealed by machine learning
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 previously published one-class logistic regression machine learning algorithm (OCLR) built on pluripotent stem cells to predict stemness in human cancer samples, we provide the stemness index (mRNAsi) of different canine non-tumor and mammary cancer cells. Then, we confirmed 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.
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