Department of Obstetrics and Gynecology Ward 2, Harbin Medical University Affiliated Second Hospital, Harbin City 150081, China.
Harbin Medical University Affiliated Second Hospital.
Crit Rev Eukaryot Gene Expr. 2024;34(5):15-29. doi: 10.1615/CritRevEukaryotGeneExpr.2024052205.
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.
RBM15 在多种癌症中作为癌基因发挥作用。然而，关于 RBM15 在宫颈癌中的作用的报道有限。本研究旨在探讨 RBM15 在宫颈癌中的潜力。采用 RT-qPCR 测定 mRNA 水平，Western blot 检测蛋白表达。CCK-8、集落形成和 EdU 检测用于评估细胞增殖，划痕和 Transwell 检测用于评估细胞迁移和侵袭。MeRIP 实验用于检测 N6-甲基腺苷（m6A）水平，荧光素酶实验用于验证 EZH2 的 m6A 位点及其与 FN1 启动子的结合位点。ChIP 实验用于验证 EZH2 与 FN1 之间的相互作用。结果表明，RBM15 在宫颈癌患者和细胞中上调。此外，高水平的 RBM15 预示着较差的临床结局。RBM15 敲低抑制了宫颈癌细胞的增殖和上皮间质转化（EMT）。RBM15 促进了 EZH2 的 m6A 修饰及其蛋白翻译。此外，EZH2 与纤维连接蛋白 1（FN1）的启动子结合，EZH2-FN1 轴是 RBM15 的级联下游。过表达的 EZH2 拮抗了 RBM15 敲低的作用，并促进了宫颈癌细胞的侵袭性。综上所述，RBM15/EZH2/FN1 信号级联诱导了宫颈癌的增殖和 EMT。因此，RBM15/EZH2/FN1 信号可能是宫颈癌的一种有前途的治疗策略。
