Investigation of the Potential Mechanisms Underlying Nuclear F-Actin Organization in Ovarian Cancer Cells by High-Throughput Screening in Combination With Deep Learning.

Investigation of the Potential Mechanisms Underlying Nuclear F-Actin Organization in Ovarian Cancer Cells by High-Throughput Screening in Combination With Deep Learning.
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DOI:
10.3389/fcell.2022.869531
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发表时间:
2022
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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越来越多的证据支持丝状肌动蛋白(F-actin)和球状肌动蛋白存在于体细胞核中的观点,并参与染色质重塑、基因转录调控和DNA损伤修复。然而,核F-肌动蛋白如何在细胞中聚合的潜在机制仍然不完全清楚。在这里,我们使用小分子抑制剂库筛选结合深度学习方法,确定了参与卵巢癌细胞核F-肌动蛋白聚合的潜在激酶靶点。对本研究中使用的抑制剂的靶点的分析表明,PI 3 K-AKT通路参与调节卵巢癌细胞中的核F-肌动蛋白组织。我们的工作为揭示核F-肌动蛋白在卵巢癌中的重要作用以及了解核F-肌动蛋白结构是如何组织的奠定了基础。
Increasing evidence supports the notion that filamentous actin (F-actin) and globular actin exist in the nuclei of somatic cells, and are involved in chromatin remodeling, gene transcription regulation and DNA damage repair. However, the underlying mechanisms of how nuclear F-actin are polymerized in cells remain incompletely understood. Here, we identify potential kinase targets that participate in nuclear F-actin polymerization in ovarian cancer cells using small-molecule inhibitor library screening in combination with a deep learning approach. The analysis of the targets of the inhibitors used in this study suggest that the PI3K-AKT pathway are involved in regulating nuclear F-actin organization in ovarian cancer cells. Our work lays the foundation for uncovering the important roles of nuclear F-actin in the context of ovarian cancer, and for understanding how nuclear F-actin structures are organized.
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