Regulation of tumorigenesis and ferroptosis in non-small cell lung cancer by a novel BBOX1-AS1/miR-326/PROM2 axis.

Autor: An J; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Shi J; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China. shijiangdoc@163.com., Yang C; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Luo J; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Li Y; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Ren J; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Lv Y; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China., Zhang Y; Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2024 Aug; Vol. 479 (8), pp. 2143-2155. Date of Electronic Publication: 2023 Aug 28.
DOI: 10.1007/s11010-023-04837-6
Abstrakt: Dysregulation of long non-coding RNAs (lncRNAs) is associated with the tumorigenesis and ferroptosis of non-small cell lung cancer (NSCLC). BBOX1 antisense RNA 1 (BBOX1-AS1) functions as an oncogenic driver in NSCLC. Here, we aim to investigate the regulation effect and underlying mechanism of BBOX1-AS1 in NSCLC progression and ferroptosis. RNA expression was detected by quantitative real-time PCR (qRT-PCR), and protein expression was measured by immunoblotting. Cell growth was assessed by CCK-8 and colony formation assays. Transwell assay was applied to evaluate cell invasion and migration. RNA pull-down and dual-luciferase reporter assays were applied to verify the relationship between miR-326 and BBOX1-AS1 or prominin 2 (PROM2). The role of BBOX1-AS1 in NSCLC tumorigenicity was also analyzed by xenograft assays. Silencing BBOX1-AS1 or PROM2 impeded NSCLC cell growth, migration, and invasion. Silencing BBOX1-AS1 induced cell apoptosis and ferroptosis. BBOX1-AS1 up-regulated PROM2 expression, and re-expression of PROM2 reversed the effects of BBOX1-AS1 depletion on cell malignant phenotypes and ferroptosis. BBOX1-AS1 post-transcriptionally modulated PROM2 expression by sponging miR-326. MiR-326 was validated as a mediator of BBOX1-AS1 in regulating NSCLC cell malignant phenotypes and ferroptosis. Additionally, BBOX1-AS1 deficiency in vivo resulted in the suppression of xenograft tumor growth. Together, our study defines a novel BBOX1-AS1/miR-326/PROM2 axis in regulating NSCLC malignant progression and ferroptosis, offering new evidence for the oncogenic role of BBOX1-AS1 in NSCLC. These findings may provide a basis for the future usage of targeting BBOX1-AS1 in NSCLC treatment.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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