RXRA induces endoplasmic reticulum stress via ATP2A3 transcriptional modulation in ovarian cancer cells

Introduction Ovarian cancer (OV) progression involves intricate interactions of genes and cellular pathways, with the ATP2A gene family recently emerging as significant. Material and methods Through bioinformatic analysis, we evaluated the expression and prognostic impact of the ATP2A gene family in various cancers, emphasizing OV. Immunohistochemical and clinical expression profiles of ATP2A2 were subsequently analyzed in OVs. We further explored the effects of ATP2A3 modulation on cellular behaviors, involving proliferation, apoptosis, migration, and invasion in OV cell lines. The function of ATP2A3 in mediating endoplasmic reticulum (ER) stress and its influence on calcium-mediated kinase activities was elucidated. Furthermore, a comprehensive analysis of The Cancer Genome Atlas (TCGA) was conducted, spotlighting the interplay between RXRA and ATP2A3. Finally, their effects on OV cell progression were analyzed in vitro. Results Our results highlighted a consistent association between low expression of ATP2A3 in OV and improved patient prognosis. ATP2A3 regulation has significant effects on the proliferation, apoptosis, migration, and invasion of OV cells. Notably, overexpression of ATP2A3 enhanced ER stress biomarkers but inhibited calcium-mediated kinase activity. At the same time, in vitro cell experiments found that RXRA overexpression can inhibit the malignant behavior of OV cells, and it is positively correlated with ATP2A3. Overexpression of RXRA inhibited OV progression by inducing the ER stress response, which was partially offset by ATP2A3. Conclusions ATP2A3 and RXRA synergistically modulate OV cell behaviors and the ER stress response, revealing prospective therapeutic avenues for OV intervention.