1. Academic Validation
  2. The m6A methyltransferase RBM15 affects tumor cell stemness and progression of cervical cancer by regulating the stability of lncRNA HEIH

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

  • Exp Cell Res. 2024 Jan 25:113924. doi: 10.1016/j.yexcr.2024.113924.
Yi Quan 1 Muchuan Zhou 2 Jinhong Li 1 Yihong Yang 1 Junliang Guo 3 Tian Tang 1 Ping Liu 1
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: jlguo@scu.edu.cn.
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.

Keywords

Cancer stem cells; Cervical cancer; N6-methyladenosine; lncRNA HEIH.

Figures
Products