KIAA1429通过介导PTGS2的m6A修饰促进鼻咽癌的进展。

IF 0.8 4区 医学 Q4 IMMUNOLOGY
Lingling Wu, Yuanhong Zhou, Jun Fu
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引用次数: 0

摘要

新出现的证据表明,N6-甲基腺苷(m6A)甲基转移酶KIAA1429的失调参与了除鼻咽癌(NPC)外的多种癌症的发病机制。本研究旨在探讨KIAA1429在鼻咽癌进展中的作用。利用癌症基因组图谱(TCGA)和基因表达综合(GEO)数据集,通过生物信息学分析证实了NPC中mRNA的表达。通过定量逆转录聚合酶链反应和蛋白质印迹检测KIAA1429和PTGS2的水平。为了研究KIAA1429/PTGS2敲低或过表达载体对NPC细胞恶性肿瘤的影响,进行了细胞和动物实验。最后,分别使用MeRIP和mRNA稳定性测定来验证m6A修饰和mRNA稳定性。KIAA1429在NPC组织和细胞中上调。在NPC细胞中转染KIAA1429敲低或过表达载体后,我们证明KIAA1429.过表达促进了增殖、迁移、侵袭和肿瘤生长,而KIAA1429-敲低显示出相反的效果。我们的结果还表明,KIAA1429介导了PTGS2的m6A修饰,增强了PTGS2mRNA在NPC细胞中的稳定性。此外,PTGS2还可以调节KIAA1429对NPC细胞恶性肿瘤的影响。本研究通过PTGS2的m6A修饰证实了KIAA1429在NPC中的致癌功能,提示靶向KIAA1429-m6A介导的PTGS2修饰可能为NPC提供一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
KIAA1429 Promotes Nasopharyngeal Carcinoma Progression by Mediating m6A Modification of PTGS2.

Emerging evidence suggests that dysregulation of a N6-methyladenosine (m6A) methyltransferase KIAA1429 participates in the pathogenesis of multiple cancers except for nasopharyngeal carcinoma (NPC). This study is aimed to explore the function of KIAA1429 in NPC progression. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to confirm the mRNA expression in NPC by bioinformatic analysis. The levels of KIAA1429 and PTGS2 was detected by quantitative reverse transcription polymerase chain reaction and Western blotting. To investigate the effects of KIAA1429/PTGS2 knockdown or overexpression vectors on NPC cell malignancy, cell and animal experiments were performed. Finally, MeRIP and mRNA stability assays were used to verify the m6A modification and mRNA stability, respectively. KIAA1429 was upregulated in NPC tissues and cells. After transfecting KIAA1429 knockdown or overexpression vectors in NPC cells, we proved that KIAA1429 overexpression promoted proliferation, migration, invasion, and tumor growth, whereas KIAA1429 knockdown showed the opposite effect. Our results also indicated that KIAA1429 mediated m6A modification of PTGS2, enhancing PTGS2 mRNA stability in NPC cells. In addition, PTGS2 could also regulate the effects of KIAA1429 on NPC cell malignancy. This study confirmed the oncogenic function of KIAA1429 in NPC through m6A-modification of PTGS2, suggesting that targeting KIAA1429-mediated m6A modification of PTGS2 might provide a new therapeutic strategy for NPC.

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来源期刊
CiteScore
2.60
自引率
0.00%
发文量
14
审稿时长
>12 weeks
期刊介绍: Immunology covers a broad spectrum of investigations at the genes, molecular, cellular, organ and system levels to reveal defense mechanisms against pathogens as well as protection against tumors and autoimmune diseases. The great advances in immunology in recent years make this field one of the most dynamic and rapidly growing in medical sciences. Critical ReviewsTM in Immunology (CRI) seeks to present a balanced overview of contemporary adaptive and innate immune responses related to autoimmunity, tumor, microbe, transplantation, neuroimmunology, immune regulation and immunotherapy from basic to translational aspects in health and disease. The articles that appear in CRI are mostly obtained by invitations to active investigators. But the journal will also consider proposals from the scientific community. Interested investigators should send their inquiries to the editor before submitting a manuscript.
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