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Cancer Lett ; 590: 216826, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38574881

ABSTRACT

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Ferroptosis , Heme Oxygenase-1 , Lung Neoplasms , RNA, Long Noncoding , Ubiquitination , Ferroptosis/genetics , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Animals , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Mice , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Female , Male , Mice, Nude , A549 Cells , Xenograft Model Antitumor Assays , Cell Proliferation
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