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

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.