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STIL Regulated by N6-Methyladenosine Methyltransferase RBM15 can Facilitate Lung Adenocarcinoma Progression
Vol 37, Issue 10, 2023
Abstract
Background: N6-methyladenosine (m6A) modification regulates gene stability, leading to the progression of lung adenocarcinoma (LUAD). However, the regulatory mechanism of the RNA-binding motif protein 15 (RBM15), an m6A methyltransferase that regulates SCL-interrupting locus protein (STIL) stability, has not yet been elucidated. This study aimed to determine the function and mechanism of action of RBM15 in LUAD. Materials and Methods: Bioinformatics analysis predicted the expression and correlation of RBM15 and STIL in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of RBM15 and STIL in clinical samples from patients with LUAD. Then, in vitro and in vivo experiments were performed to confirm the effects of RBM15 and STIL on the progression of LUAD. Finally, Methylated RNA Immunoprecipitation, mRNA stability, qRT-PCR, and western blotting were performed to identify the correlation between RBM15 and STIL in LUAD cells. Results: RBM15 was confirmed to be upregulated in LUAD, and its knockdown inhibited LUAD malignancy by decreasing proliferation, migration, and invasion. In vivo experiments confirmed that RBM15 knockdown inhibited tumor growth. RBM15 knockdown reduces STIL stability via m6A modification. Additionally, STIL overexpression contributed to the malignancy of LUAD cells; however, RBM15 knockdown partly relieved this effect. Conclusion: RBM15 knockdown suppresses LUAD progression by reducing STIL stability. This may provide novel biomarkers for the diagnosis and therapy of LUAD.
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Copyright (c) 2023 Chunyan Li, Zhiwen Huang
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy