Abstract
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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide[1]
Previous studies have established the CpG island hypermethylation phenotype (CIMP) as a hallmark in many cancer types; here we aimed to focus on studying hypermethylated Long noncoding RNAs (lncRNAs)
Methylation intensity of epigenetically silenced lncRNAs is enriched near TSS (Fig. 1b), which is consistent with the notion that hypermethylation of a gene promoter suppresses its transcription
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide[1]. Despite progresses achieved in therapies, such as using nivolumab and pembrolizumab to target the programmed cell death protein 1 (PD-1) in advanced HNSCC, the overall 5-year survival rate for patients with HNSCC remains unsatisfactory, which is below 50%. Progression is essential for improving HNSCC treatment. The results from human genome sequencing projects indicate that protein-coding sequences occupy less than 2% of the human genome[3]. Long noncoding RNAs (lncRNAs) refer to a class of RNA transcripts longer than 200 nucleotides with limited protein-coding potential. Aberrant expression of lncRNAs has been associated with the occurrence and development of various types of cancers[4], including HNSCC. LncRNA can act as “sponges” to titrate microRNAs
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