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POU2F2-mediated Upregulation of lncRNA <i>PTPRG-AS1</i> Inhibits Ferroptosis in Breast Cancer Via miR-376c-3p/SLC7A11 Axis

Jun Li, Pei-Ting Li, Wei Wu, B. Ding, Yanguang Wen, H. Cai, Sitao Liu, Tao Hong, Jian-Fei Zhang, Jian-Da Zhou, Liyuan Qian, Du Juan

2024Epigenomics18 citationsDOI

Abstract

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

Topics & Concepts

BiologyDownregulation and upregulationTriple-negative breast cancerMolecular biologyCancer researchGene knockdownCancerBiochemistryApoptosisBreast cancerGeneGeneticsCancer-related molecular mechanisms researchFerroptosis and cancer prognosisCancer, Lipids, and Metabolism