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The m6A methyltransferase RBM15 affects tumor cell stemness and progression of cervical cancer by regulating the stability of lncRNA HEIH
Experimental Cell Research ( IF 3.7 ) Pub Date : 2024-01-26 , DOI: 10.1016/j.yexcr.2024.113924
Yi Quan , Muchuan Zhou , Jinhong Li , Yihong Yang , Junliang Guo , Tian Tang , Ping Liu

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 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.

中文翻译:

m6A甲基转移酶RBM15通过调节lncRNA HEIH的稳定性影响肿瘤细胞干细胞和宫颈癌的进展

宫颈癌(CC)作为全球常见的女性恶性肿瘤,是危害全球女性健康的重要危险因素。本研究的目的是探讨 RBM15 在 CC 中的作用。利用TCGA数据库筛选正常组织和肿瘤组织中差异表达的m6A基因。 QRT-PCR 用于定量 HEIH、miR-802、EGFR、细胞干性和上皮间质转化 (EMT) 相关基因。通过双荧光素酶报告基因测定和 RIP 测定验证了 HEIH 和 miR-802 之间的相互作用。通过CCK-8、Transwell和EdU染色检测不同处理后肿瘤细胞的发生情况。 BALB/c裸鼠用于检测不同治疗对肿瘤生长和细胞干性的影响RBM15在肿瘤组织和细胞中上调。 M6A 在 HEIH 中高度富集并增强其 RNA 稳定性。 HEIH 作为致癌 lncRNA,促进 CC 细胞增殖、迁移和肿瘤生长。机制上,HEIH通过竞争性吸附miR-802和上调EGFR表达来调节肿瘤细胞干性并促进CC细胞的增殖和迁移。简而言之,我们的数据表明m6A甲基转移酶RBM15可以通过稳定HEIH表达来影响肿瘤细胞增殖、转移和细胞干性。
更新日期:2024-01-26
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