RBM15 functions as an oncogene in multi-type cancers. However, the reports on the roles of RBM15 in cervical cancer are 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, colony formation and EdU assays were conducted to determine cell proliferation. Scratch and transwell assays were conducted 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 EZH2 and promoter of FN1. ChIP assay was conducted to verify the interaction between EZH2 and FN1. The results showed that RBM15 was upregulated in cervical cancer patients and cells. Moreover, high levels of RBM15 predicted poor clinical outcomes. 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 axis is the cascade downstream of RBM15. Overexpressed EZH2 antagonized the effects of RBM15 knockdown and promoted the aggressiveness of cervical cancer cells. 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.

中文翻译：

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

RBM15 在多种癌症中充当癌基因。然而，关于RBM15在宫颈癌中的作用的报道有限。本研究的目的是探讨 RBM15 在宫颈癌中的潜力。进行 RT-qPCR 以确定 mRNA 水平。进行Western检测蛋白表达。进行 CCK-8、集落形成和 EdU 测定以确定细胞增殖。进行划痕和跨孔实验以确定细胞迁移和侵袭。进行 MeRIP 测定以确定 N6-甲基腺苷 (m6A) 水平。进行荧光素酶测定以验证EZH2的m6A位点以及EZH2与FN1启动子之间的结合位点。进行 ChIP 测定以验证 EZH2 和 FN1 之间的相互作用。结果表明，RBM15在宫颈癌患者和细胞中表达上调。此外，高水平的 RBM15 预示着较差的临床结果。 RBM15敲低抑制宫颈癌细胞的增殖和上皮间质转化（EMT）。 RBM15 促进 EZH2 的 m6A 修饰及其蛋白质翻译。此外，EZH2 与纤连蛋白 1 (FN1) 启动子和 EZH2-FN1 轴结合是 RBM15 的级联下游。过表达的 EZH2 拮抗 RBM15 敲低的作用并促进宫颈癌细胞的侵袭性。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信号传导可能是治疗宫颈癌的一个有前途的策略。