Li Ruiying, Xia Xiaochuang, Chen Wenping, Wang Hongmin, Feng Lunda, Wang Zhouyi
Department of Geriatrics, Huanggang Central Hospital, No.126, Huangzhou District, Huanggang, 438000, Hubei, China.
Department of Cardiovascular Medicine, Huanggang Central Hospital, Huanggang 438000, Hubei, China.
Mol Biotechnol. 2024 Nov 18. doi: 10.1007/s12033-024-01323-2.
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.
P53凋亡效应因子相关蛋白22（PERP）对肺腺癌（LUAD）的促进作用已得到证实。然而，PERP的N6-甲基腺苷（m6A）修饰在调节LUAD进展中的作用尚未见报道。利用GEPIA和癌症基因组图谱（TCGA）数据库进行生物信息学分析，预测了PERP与RBM15及p53信号通路相互作用的机制。应用qRT-PCR、细胞功能实验和蛋白质免疫印迹法进一步证实PERP和RBM15在LUAD细胞中的功能及机制。采用甲基化RNA免疫沉淀（MeRIP）和mRNA稳定性检测来揭示LUAD细胞中PERP与RBM15的相互作用。PERP在LUAD中高表达提示患者预后不良。沉默PERP可通过激活p53信号通路抑制LUAD细胞的增殖、迁移和侵袭，而过表达PERP则对LUAD细胞产生相反的作用。机制上，RBM15过表达可促进PERP的m6A修饰，增强PERP mRNA的稳定性。此外，PERP敲低可逆转RBM15过表达导致的LUAD细胞恶性表型。本研究揭示了RBM15调控的PERP的m6A修饰通过抑制p53信号通路增强LUAD的肿瘤发生，这可能为LUAD的发病机制提供新的见解。
