» Articles » PMID: 39556280

N6-Methyladenosine Modification of PERP by RBM15 Enhances the Tumorigenesis of Lung Adenocarcinoma Via P53 Signaling Pathway

Overview
Journal Mol Biotechnol
Publisher Springer
Date 2024 Nov 18
PMID 39556280
Authors
Affiliations
Soon will be listed here.
Abstract

The promotive effect of P53 apoptosis effector related to PMP-22 (PERP) on lung adenocarcinoma (LUAD) has been confirmed. However, the N6-methyladenosine (m6A) modification of PERP to regulate LUAD progression have not been revealed. Bioinformatic analysis predicted the mechanism of PERP interacting with RBM15 and p53 pathway using GEPIA and The Cancer Genome Atlas (TCGA) databases. The qRT-PCR, cell function experiments, and western blotting were applied to further confirm the function and mechanism of PERP and RBM15 in LUAD cells. Methylated RNA immunoprecipitation (MeRIP) and mRNA stability assays were used to reveal the interaction between PERP and RBM15 in LUAD cells. PERP with high expression in LUAD showed the poor survival. Silencing PERP prevented LUAD cells to proliferate, migrate, and invade via activating p53 pathway, whereas overexpressing PERP showed the opposite effect on LUAD cells. Mechanistically, RBM15 overexpression could promote PERP m6A modification to enhance the PERP mRNA stability. In addition, RBM15 overexpression leading to LUAD cell malignancy was reversed by PERP knockdown. This study reveals that the mA modification of PERP regulated by RBM15 enhances the tumorigenesis of LUAD by inhibiting the p53 signaling pathway, which may provide novel insights into the LUAD mechanism.

References
1.
Zappa C, Mousa S . Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016; 5(3):288-300. PMC: 4931124. DOI: 10.21037/tlcr.2016.06.07. View

2.
Jurisic V, Vukovic V, Obradovic J, Gulyaeva L, Kushlinskii N, Djordjevic N . Polymorphism and Survival of NSCLC Patients Treated with TKIs: A Systematic Review and Meta-Analysis. J Oncol. 2020; 2020:1973241. PMC: 7104312. DOI: 10.1155/2020/1973241. View

3.
Lam D, Liam C, Andarini S, Park S, Tan D, Singh N . Lung Cancer Screening in Asia: An Expert Consensus Report. J Thorac Oncol. 2023; 18(10):1303-1322. DOI: 10.1016/j.jtho.2023.06.014. View

4.
Dusek R, Attardi L . Desmosomes: new perpetrators in tumour suppression. Nat Rev Cancer. 2011; 11(5):317-23. PMC: 3799918. DOI: 10.1038/nrc3051. View

5.
Dusek R, Bascom J, Vogel H, Baron S, Borowsky A, Bissell M . Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer. Breast Cancer Res. 2012; 14(2):R65. PMC: 3446400. DOI: 10.1186/bcr3171. View