RBM15-mediated N6-methyl adenosine (m6A) modification of EZH2 drives the epithelial-mesenchymal transition of cervical cancer

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-02-01 DOI:10.1615/critreveukaryotgeneexpr.2024052205

Ruixue Wang, Wenhua Tan

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Abstract

RBM15 functions as an oncogene in multi-type cancers. However, the report on the roles of RBM15 in cervical cancer is limited. The purpose of this study was to investigate the potentials of RBM15 in cervical cancer. RT-qPCR was conducted to determine mRNA levels. Western was carried out to detect protein expression. CCK-8 and colony formation assays were carried out to determine cell proliferation. Scratch and transwell assays were carried out to determine cell migration and invasion. MeRIP assay was conducted to determine N6-methyl adenosine (m6A) levels. Luciferase assay was conducted to verify the m6A sites of EZH2 and binding sites between cc and promoter of FN1. ChIP assay was conducted to verify the interaction between EZH2 and FN1. RBM15 was upregulated in cervical cancer tissues and cells. Moreover, high levels of RBM15 predicted poor clinical outcomes of cervical cancer patients. RBM15 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. RBM15 promoted the m6A modification of EZH2 as well as its protein translation. Additionally, EZH2 bound to the promoter of fibronectin 1 (FN1) and EZH2-FN1 is the cascade downstream of RBM15. Overexpressed EZH2 antagonized the effects of RBM15 knockdown and promoted the aggressiveness of cervical cancer. In summary, RBM15/EZH2/FN1 signaling cascade induces the proliferation and EMT of cervical cancer. Therefore, RBM15/EZH2/FN1 signaling may be a promising strategy for cervical cancer.

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RBM15介导的EZH2的N6-甲基腺苷（m6A）修饰驱动宫颈癌的上皮-间质转化

RBM15 在多类型癌症中发挥着癌基因的作用。然而，有关 RBM15 在宫颈癌中作用的报道却很有限。本研究旨在探讨 RBM15 在宫颈癌中的潜在作用。研究采用 RT-qPCR 方法测定 mRNA 水平。采用 Western 方法检测蛋白质表达。通过 CCK-8 和菌落形成试验确定细胞增殖情况。进行划痕和透孔试验以确定细胞迁移和侵袭。进行 MeRIP 检测以确定 N6-甲基腺苷（m6A）水平。通过荧光素酶检测来验证 EZH2 的 m6A 位点以及 cc 与 FN1 启动子之间的结合位点。通过 ChIP 检测来验证 EZH2 与 FN1 之间的相互作用。RBM15在宫颈癌组织和细胞中上调。此外，高水平的RBM15预示着宫颈癌患者的不良临床预后。敲除 RBM15 可抑制宫颈癌细胞的增殖和上皮-间质转化（EMT）。RBM15 促进了 EZH2 的 m6A 修饰及其蛋白质翻译。此外，EZH2还与纤连蛋白1（FN1）的启动子结合，EZH2-FN1是RBM15下游的级联。过表达的 EZH2 可拮抗 RBM15 敲除的作用，并促进宫颈癌的侵袭性。综上所述，RBM15/EZH2/FN1 信号级联诱导宫颈癌的增殖和 EMT。因此，RBM15/EZH2/FN1 信号转导可能是治疗宫颈癌的一种有前景的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

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审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.