Expression and Prognostic Significance of the m6A RNA Methylation Regulator HNRNPC in HNSCC

Abstract

Abstract Background N6-methyladenosine (m6A) RNA modification is crucial for tumor development and progression; however, which m6A regulators play a pivotal role in head and neck squamous cell carcinoma (HNSCC) remains ambiguous. Methods Utilizing the Cancer Genome Atlas (TCGA) database, the expression levels of m6A regulators in HNSCC were examined, which led to the identification of heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a key gene. Further experiments were performed in patient samples, stable cell lines, and a murine xenograft tumor model. Results A reliable survival risk model of m6A was constructed based on the TCGA database, which revealed that HNRNPC had the highest expression. TCGA, Gene Expression Omnibus (GEO), normal and tumor tissue microarrays (TMA), and tumor tissue samples from patients with HNSCC were used to verify the expression of HNRNPC at the mRNA and protein levels. Furthermore, we observed that a high level of HNRNPC expression was closely linked to a poor prognosis among patients with HNSCC. Knockdown of HNRNPC in the HNSCC cell lines HSC-3 and CAL-27 resulted in a significant decrease in proliferation, invasion, and malignant transformation abilities. RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation and sequencing (MeRIP-seq) data revealed that HNRNPC is involved in cell differentiation, cell migration, cell cycle, cell proliferation, and apoptosis. Moreover, we utilized a mouse xenograft model to elucidate that HNRNPC can promote tumorigenesis and progression of HNSCC. Conclusions HNRNPC can serve as a valuable predictor of tumor progression and prognosis in patients with HNSCC.