Epigenetic regulation of VENTXP1 suppresses tumor proliferation via miR-205-5p/ANKRD2/NF-kB signaling in head and neck squamous cell carcinoma

• Published in: Cell death & disease Vol. 11; no. 10; p. 838
• Main Authors: Zhang, Li Ming, Su, Li Xin, Hu, Jing Zhou, Wang, De Ming, Ju, Hou Yu, Li, Xiao, Han, Yi Feng, Xia, Wei Ya, Guo, Wei, Ren, Guo Xin, Fan, Xin Dong
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group UK 09.10.2020
• Subjects: Carcinoma, Squamous Cell - genetics; Cell Movement - genetics; Cell Proliferation - genetics; Epigenesis, Genetic - genetics; Gene Expression Regulation, Neoplastic - genetics; Head and Neck Neoplasms - genetics; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; MicroRNAs - genetics; Muscle Proteins - genetics; NF-kappa B - metabolism; Nuclear Proteins - genetics; Repressor Proteins - genetics; RNA, Long Noncoding - genetics; Signal Transduction; Squamous Cell Carcinoma of Head and Neck - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-03057-w

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in tumor development and progression. However, their involvement in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Epigenetic regulation is one major mechanism utilized by cancer cells to control lncRNA expression. We identified that lncRNA VENTXP1 was epigenetically silenced in multiple cancer types, and its lower expression was correlated with poorer survival in HNSCC patients. Through in silico analysis and experimental validation, we identified miR-205-5p and its direct interacting partner of VENTXP1, which regulates HNSCC cell proliferation and tumorigenicity. Using RNA-seq and differential gene expression analysis, we further identified ANKRD2 as a miR-205-5p target, which plays an essential role in modulating NF-kB signaling. These findings suggest that VENTXP1 inhibits tumor growth via suppressing miR-205-5p/ANKRD2-mediated NF-kB signaling in HNSCC. Thus, pharmaceutical targeting of DNA methylation to restore VENTXP1 expression might constitute a therapeutic strategy for HNSCC.