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

• Published in: Molecular and cellular biochemistry 2024-08, Vol.479 (8), p.2143-2155
• Main Authors: An, Jinlu, Shi, Jiang, Yang, Chao, Luo, Junfang, Li, Yuning, Ren, Jie, Lv, Yuanjun, Zhang, Yang
• Format: Article
• Language: English
• Subjects: Animals; Antisense RNA; Apoptosis; Assaying; Biochemistry; Biomedical and Life Sciences; Cancer Research; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cardiology; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Cholecystokinin; Ferroptosis; Ferroptosis - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; In vivo methods and tests; Life Sciences; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical Biochemistry; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Non-small cell lung carcinoma; Phenotypes; Polymerase chain reaction; Post-transcription; Real time; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Small cell lung carcinoma; Tumorigenesis; Tumorigenicity; Xenografts; Xenotransplantation
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-023-04837-6

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.