The m6A methyltransferase RBM15 affects tumor cell stemness and progression of cervical cancer by regulating the stability of lncRNA HEIH

m6A 甲基转移酶 RBM15 通过调节 lncRNA HEIH 的稳定性影响肿瘤细胞干性和宫颈癌进展

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作者:Yi Quan, Muchuan Zhou, Jinhong Li, Yihong Yang, Junliang Guo, Tian Tang, Ping Liu

Abstract

Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering women's health worldwide. The purpose of this study was to investigate the role of RBM15 in CC. The TCGA database was used to screen differentially expressed m6A genes in normal and tumor tissues. QRT-PCR was used to quantify HEIH, miR-802, EGFR, cell stemness, and epithelial-mesenchymal transition (EMT)-related genes. The interaction between HEIH and miR-802 was verified by dual-luciferase reporter assay and RIP assay. The occurrence of tumor cells after different treatments was detected by CCK-8, transwell and EdU staining. BALB/c nude mice were used to examine the effects of different treatments on tumor growth and cell stemness in vivo. RBM15 was upregulated in tumor tissues and cells. M6A was highly enriched in HEIH and enhances its RNA stability. HEIH acts as an oncogenic lncRNA to promote CC cell proliferation, migration and tumor growth. Mechanistically, HEIH regulates tumor cell stemness and promotes the proliferation and migration of CC cells by competitively adsorbing miR-802 and up-regulating the expression of EGFR. In short, our data shown that the m6A methyltransferase RBM15 could affect tumor cell proliferation, metastasis and cell stemness by stabilizing HEIH expression.

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