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

Front Cell Dev Biol. 2022 May 26:10:869531. doi: 10.3389/fcell.2022.869531. eCollection 2022.

Abstract

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.

Keywords: deep learning; high-throughput screening; kinase; nuclear F-actin; ovarian cancer.