@Article{or.2025.063700,
AUTHOR = {Xiaobing Zhou, Ying Li, Zizi Jing, Wei Yu, Jianbin Chen},
TITLE = {ERRγ Promotes Multiple Myeloma Survival by Coordinating NF-κB Signaling and Mitochondrial Apoptosis Regulation},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {9},
PAGES = {2399--2420},
URL = {http://www.techscience.com/or/v33n9/63623},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Multiple myeloma (MM) remains a formidable clinical challenge due to its high relapse rate and resistance to existing therapies. Estrogen-related receptor gamma (ERRγ), a nuclear receptor critical for cellular energy metabolism, has been implicated in various cancers. but its role in MM remains unclear. <b>Methods:</b> ERRγ expression was assessed using bioinformatics and RT-qPCR. Functional studies were conducted through siRNA-mediated ERRγ knockdown and treatment with the inverse agonist GSK5182 to examine their effects on MM cell proliferation and apoptosis. <b>Results:</b> ERRγ was significantly upregulated in the bone marrow of MM patients, correlating with advanced clinical stages and pathological fractures. Inhibition of ERRγ reduced MM cell expansion both <i>in vitro</i> and <i>in vivo</i>, while promoting mitochondrial-dependent apoptosis. Co-immunoprecipitation assays demonstrated a physical association between ERRγ and P65. Inhibition of ERRγ attenuated canonical nuclear factor-kappa B (NF-κB) signaling by blocking the nuclear translocation of its key effector p65. Additionally, modulation of ERRγ altered receptor activator of nuclear factor-κB ligand (RANKL) levels, implying a potential role in bone degradation observed in MM cases. <b>Conclusion:</b> Collectively, the data broaden understanding of ERRγ’s contribution to MM development and propose it as a viable target for therapeutic intervention.},
DOI = {10.32604/or.2025.063700}
}