DDX60 Promotes Migration and Invasion of Head and Neck Squamous Cell Carcinoma Cell through the NF-κB/IFI27 Signaling Pathway

Background: Despite its significance in multiple cancer types. the function and mechanism of DEXD/H box helicase 60 (DDX60) in head and neck squamous cell carcinoma (HNSCC) remain unreported. Methods: Thirty paired HNSCC tissues and adjoining normal tissues and human normal oral epithelial keratinocytes (HOK) and four HNSCC cells (CAL27, SAS, CAL33, and SCC25) were analyzed for DDX60 expression by Semi-quantitative real-time PCR (SQ RT-PCR) and western blot. To investigate how DDX60 affects HNSCC cell migration and invasion, transwell experiments were performed. The western blot was implemented to understand the interaction among DDX60, Interferon Alpha Inducible Protein 27 (IFI27), and the NF- $\kappa{}$ B pathway. Results: Results revealed the upregulation of DDX60 in HNSCC cell lines and tissues. Additionally, patients with upregulated DDX60 expression exhibited a dismal prognosis relative to those with downregulated expression. DDX60 enhanced the migration, invasion, and epithelial to mesenchymal transition (EMT) in HNSCC cells. The results from mechanistic studies revealed that DDX60 could promote the IFI27 expression following the activation of NF- $\kappa{}$ B pathway. Conclusion: DDX60 promoted the migratory and invasive capacities of HNSCC cells via the NF- $\kappa{}$ B/IFI27 axis.

Keywords

head and neck squamous cell carcinoma

DDX60

EMT

NF-

\kappa{}

B pathway

IFI27

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Fig. 1.

DEXD/H box helicase 60 (DDX60) expression was upregulated in HNSCC tissues and cells. (A) Analysis results of the data from the GEPIA database show that DDX60 was upregulated in DLBC, ESCA, GBM, HNSCC, LAML, LGG, PAAD, and THYM. (B) Analysis results of the data from the ENCORI database confirmed that DDX60 was upregulated in HNSCC. (C,D) Survival curves of patients with HNSCC predicted by the GEPIA database (C) and ENCORI database (D) based on the mRNA levels of DDX60. (E) The mRNA levels of DDX60 in 30 pairs of HNSCC and its paraneoplastic tissues were detected by SQ RT-PCR. (F) The DDX60 expression levels in 4 pairs of HNSCC and its paraneoplastic tissues were detected by western blot. (G,H) The DDX60 mRNA and protein levels in human normal oral epithelial keratinocytes (HOK) and four HNSCC cells (CAL27, SAS, CAL33, and SCC25) were detected by SQ RT-PCR (G) and western blot (H). *p $<$ 0.05, **p $<$ 0.01, ***p $<$ 0.001, ****p $<$ 0.0001. DLBC, Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, Esophageal carcinoma; GBM, Glioblastoma; HNSCC, Head and neck squamous cell carcinoma; LAML, Acute myeloid leukemia; LGG, Lower-grade glioma; PAAD, Pancreatic adenocarcinoma; THYM, Thymoma; mRNA, messenger RNA; SQ RT-PCR, Semi-Quantitative Real-Time PCR; GEPIA, Gene Expression Profiling Interactive Analysis.

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Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698