POU2F2-mediated upregulation of lncRNA PTPRG-AS1 inhibits ferroptosis in breast cancer via miR-376c-3p/SLC7A11 axis

Author:

Li Jun1ORCID,Li Pei-Ting1ORCID,Wu Wei1ORCID,Ding Bo-Ni1ORCID,Wen Yan-Guang1ORCID,Cai Hai-Lin1ORCID,Liu Shuang-Xi1ORCID,Hong Tao2ORCID,Zhang Jian-Fei3ORCID,Zhou Jian-Da4ORCID,Qian Li-Yuan1ORCID,Du Juan1ORCID

Affiliation:

1. Department of Breast & Thyroid Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China

2. Department of Breast & Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, China

3. Department of Plastic Surgery, The Second Affiliated Hospital of the University of South China, Hengyang, 421000, Hunan Province, China

4. Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China

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.

Publisher

Informa UK Limited

Subject

Cancer Research,Genetics

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