N6-Methyladenosine Modification of PERP by RBM15 Enhances the Tumorigenesis of Lung Adenocarcinoma via p53 Signaling Pathway.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Biotechnology Pub Date : 2024-11-18 DOI:10.1007/s12033-024-01323-2

Ruiying Li, Xiaochuang Xia, Wenping Chen, Hongmin Wang, Lunda Feng, Zhouyi Wang

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引用次数: 0

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 m⁶A 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.

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RBM15对PERP的N6-甲基腺苷修饰可通过p53信号通路增强肺腺癌的肿瘤发生能力

与 PMP-22 相关的 P53 细胞凋亡效应因子（PERP）对肺腺癌（LUAD）的促进作用已被证实。然而，PERP 的 N6-甲基腺苷（m6A）修饰对 LUAD 进展的调控作用尚未被揭示。生物信息学分析利用 GEPIA 和癌症基因组图谱（TCGA）数据库预测了 PERP 与 RBM15 和 p53 通路的相互作用机制。为了进一步证实PERP和RBM15在LUAD细胞中的功能和机制，研究人员采用了qRT-PCR、细胞功能实验和Western印迹等方法。甲基化RNA免疫沉淀（MeRIP）和mRNA稳定性实验揭示了PERP和RBM15在LUAD细胞中的相互作用。高表达的PERP在LUAD中存活率很低。沉默 PERP 可通过激活 p53 通路阻止 LUAD 细胞增殖、迁移和侵袭，而过表达 PERP 则对 LUAD 细胞产生相反的影响。从机理上讲，RBM15的过表达可促进PERP m6A的修饰，从而增强PERP mRNA的稳定性。此外，RBM15过表达导致LUAD细胞恶性化的情况可被PERP敲除逆转。本研究揭示了RBM15调控的PERP m6A修饰通过抑制p53信号通路增强了LUAD的肿瘤发生，这可能为LUAD的机制提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Biotechnology 医学-生化与分子生物学

CiteScore

4.10

自引率

3.80%

发文量

165

审稿时长

6 months

期刊介绍： Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.