KIAA1429-mediated RXFP1 attenuates non-small cell lung cancer tumorigenesis via N6-methyladenosine modification.

IF 2.2 4区医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2024-02-07 DOI:10.3233/CBM-230188

Zhixiang Zhang, Jipeng Guo, Chongwen Gong, Sai Wu, Yanlei Sun

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Abstract

Background: N6-methyladenosine (m6A) modification has been associated with non-small cell lung cancer (NSCLC) tumorigenesis.

Objectives: This study aimed to determine the functions of Vir-like m6A methyltransferase-associated (KIAA1429) and relaxin family peptide receptor 1 (RXFP1) in NSCLC.

Methods: A quantitative real-time polymerase chain reaction was used to analyze the mRNA levels of KIAA1429 and RXFP1 in NSCLC. After silencing KIAA1429 or RXFP1 in NSCLC cells, changes in the malignant phenotypes of NSCLC cells were assessed using cell counting kit-8, colony formation, and transwell assays. Finally, the m6A modification of RXFP1 mediated by KIAA1429 was confirmed using luciferase, methylated RNA immunoprecipitation, and western blot assays.

Results: KIAA1429 and RXFP1 were upregulated and downregulated in NSCLC, respectively. Silencing of KIAA1429 attenuated the viability, migration, and invasion of NSCLC cells, whereas silencing of RXFP1 showed the opposite function in NSCLC cells. Moreover, RXFP1 expression was inhibited by KIAA1429 via m6A-modification. Therefore, silencing RXFP1 reversed the inhibitory effect of KIAA1429 knockdown in NSCLC cells.

Conclusion: Our findings confirmed that the KIAA1429/RXFP1 axis promotes NSCLC tumorigenesis. This is the first study to reveal the inhibitory function of RXFP1 in NSCLC via KIAA1429-mediated m6A-modification. These findings may help identify new biomarkers for targeted NSCLC therapy.

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KIAA1429 介导的 RXFP1 通过 N6-甲基腺苷修饰减轻非小细胞肺癌的肿瘤发生。

背景：N6-甲基腺苷（m6A）修饰与非小细胞肺癌（NSCLC）的肿瘤发生有关：本研究旨在确定病毒样m6A甲基转移酶相关（KIAA1429）和弛缓素家族肽受体1（RXFP1）在NSCLC中的功能：方法：采用实时定量聚合酶链反应分析NSCLC中KIAA1429和RXFP1的mRNA水平。在NSCLC细胞中沉默KIAA1429或RXFP1后，使用细胞计数试剂盒-8、集落形成和透孔试验评估NSCLC细胞恶性表型的变化。最后，利用荧光素酶、甲基化 RNA 免疫沉淀和 Western 印迹检测法证实了 KIAA1429 介导的 RXFP1 m6A 修饰：结果：KIAA1429和RXFP1在NSCLC中分别上调和下调。KIAA1429和RXFP1在NSCLC细胞中分别出现上调和下调，沉默KIAA1429可减轻NSCLC细胞的活力、迁移和侵袭，而沉默RXFP1则显示出相反的作用。此外，KIAA1429通过m6A修饰抑制了RXFP1的表达。因此，沉默RXFP1可逆转KIAA1429敲除对NSCLC细胞的抑制作用：我们的研究结果证实，KIAA1429/RXFP1轴促进了NSCLC的肿瘤发生。这是首次揭示 RXFP1 通过 KIAA1429 介导的 m6A 修饰在 NSCLC 中的抑制功能的研究。这些发现可能有助于确定NSCLC靶向治疗的新生物标记物。

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

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.