Abstract 2962: The oncogenic role of epigenetic factor, SNF2L in PCa

Abstract

Abstract Prostate cancer (PCa) is the second-leading cause of cancer mortality in the United States and is the most commonly diagnosed malignancy in African American men. Epigenetic regulation including chromatin remodeling plays a crucial role in the development and progression of many human diseases such as cancers. Epigenetic alterations contribute to the development and progression of PCa. These alterations may cause drug resistance to readily available treatment options for human cancers including PCa. Nucleosome-remodeling factor (NURF) consists of bromodomain-PHD finger transcription factor (BPTF), sucrose non-fermenting-2-like (SNF2L), and pRBAP46/48, controls the chromatin remodeling machinery. One of NURF’s major function is to regulate histone modifications and gene expression. Epigenetic factor, SNF2L, serves as the energy transducing subunit in NURF and is encoded by the SMARCA1 gene. SNF2L is a ubiquitously expressed transcription activator and its elevation is associated with cancer development. However, the role of SNF2L on PCa progression is still elusive. Therefore, there are unmet needs to understand the role of SNF2L in PCa in order to develop effective therapeutic approaches of controlling this malignancy. The objective of this project is to assess the impact of SNF2L loss on PCa progression. We hypothesized that SNF2L knockout (KO) will inhibit the proliferation of androgen-sensitive and castration-resistant PCa cells and targeting SNF2L or SMARCA-1 gene may be beneficial for controlling cancer progression. We have generated SNF2L KO PCa cells with CRISPR-Cas9 technology and inhibited SMARCA-1 gene via transient transfection application. Our results showed that SNF2L loss resulted in a reduced proliferation and altered morphology of PCa cells. SNF2L KO destabilizes the NURF complex and impairs chromatin remodeling and histone modifications for cell growth and survival. Thereby, targeting SNF2L may serve as a novel therapeutic regime in PCa control. Citation Format: LaKendria K. Brown, Guoliang Li, Thanigaivelan Kanagasabai, Zhenbang Chen. The oncogenic role of epigenetic factor, SNF2L in PCa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2962.