Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, PR China; Sichuan Provincial Key Laboratory of Development and Related Diseases of Women and Children, Chengdu, 610041, Sichuan, PR China.
Department of Anesthesia, Sichuan Integrative Medicine Hospital, Sichuan Academy of Chinese Medicine Science (SACMS), Chengdu, 610000, PR China; Sichuan Provincial Key Laboratory of Quality of Chinese Medicinal Materials and Research on Innovative Chinese Medicine, Chengdu, 610041, Sichuan, PR China.
Exp Cell Res. 2024 Mar 15;436(2):113924. doi: 10.1016/j.yexcr.2024.113924. Epub 2024 Jan 26.
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.
宫颈癌（CC）作为世界范围内常见的女性恶性肿瘤，是威胁全球女性健康的重要危险因素。本研究旨在探讨 RBM15 在 CC 中的作用。我们使用 TCGA 数据库筛选正常组织和肿瘤组织中差异表达的 m6A 基因。使用 qRT-PCR 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检测和 RIP 实验验证 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 裸鼠用于体内检测不同处理对肿瘤生长和细胞干性的影响。结果表明，RBM15 在肿瘤组织和细胞中上调。HEIH 中 m6A 高度富集，增强其 RNA 稳定性。HEIH 作为致癌 lncRNA 通过竞争性吸附 miR-802 并上调 EGFR 的表达来促进 CC 细胞增殖、迁移和肿瘤生长。总之，我们的数据表明，m6A 甲基转移酶 RBM15 可以通过稳定 HEIH 的表达来影响肿瘤细胞的增殖、转移和细胞干性。
