Novel roles for HMGA2 isoforms in regulating oxidative stress and sensitizing to RSL3-Induced ferroptosis in prostate cancer cells

• DOI: 10.1016/j.heliyon.2023.e14810
• Publication Date: 2023-04-07T06:20:50Z
• Authors: Taaliah Campbell; Ohuod Hawsawi; Veronica Henderson; Precious Dike; Bor-Jang Hwang; Yusuf Liadi; ElShaddai Z. White; Jin Zou; GuangDi Wang; Qiang Zhang; Nathan Bowen; Derrick Scott; Cimona V. Hinton; Valerie Odero-Marah
• Keywords: HMGA2

Oxidative stress is increased in several cancers including prostate cancer, and currently being exploited cancer therapy to induce ferroptosis, a novel nonapoptotic form of cell death. High mobility group A2 (HMGA2), non-histone protein up-regulated cancers, can be truncated due chromosomal rearrangement or alternative splicing HMGA2 gene. The purpose this study investigate the role wild-type vs. (PCa). We analyzed expression showed that patient tissue some lines expressed increasing amounts both with tumor grade, compared normal epithelial cells. RNA-Seq analysis LNCaP cells stably overexpressing (HMGA2-WT), (HMGA2-TR) empty vector (Neo) control revealed HMGA2-TR exhibited higher oxidative HMGA2-WT Neo cells, which was also confirmed by basal reactive oxygen species (ROS) levels using 2', 7'-dichlorofluorescin diacetate (DCFDA) dye, ratio reduced glutathione/oxidized glutathione (GSH/GSSG) NADP/NADPH metabolomics. This associated sensitivity RAS-selective lethal 3 (RSL3)-induced ferroptosis could antagonized ferrostatin-1. Additionally, proteomic immunoprecipitation analyses cytoplasmic interacted Ras GTPase-activating protein-binding 1 (G3BP1), granule responds stress, G3BP1 transient knockdown even further. Endogenous PC3 proliferation reversed In conclusion, we show for particularly HMGA2, may therapeutic target ferroptosis-mediated therapy.