Role of ubiquitin-specific peptidase 22 in carcinogenesis of human pharyngeal squamous cell carcinoma.

Abstract

Human pharyngeal squamous cell carcinoma (HNSCC) are highly invasive and proliferative and exhibit a poor five-year survival rate, mainly due to poor understanding of HNSCC pathogenesis mechanisms, preventing efficient treatment. Ubiquitin‑specific peptidase 22 (USP22) is an important component of cell cycle regulation, as it indirectly affects chromatin structure via histone ubiquitination and regulates activation of gene transcription. In previous studies, silencing of USP22 significantly inhibited tumor cell proliferation. To investigate the expression levels and the role of USP22 in the carcinogenesis of human pharyngeal squamous cell carcinoma, pharyngeal squamous cell carcinoma and adjacent normal tissue samples were collected from four patients. Six pharyngeal squamous cell carcinoma cell lines (SAS, CAL-33, FaDu, HSC-4, UTSCC-5 and UTSCC-8) were also included in this study. The USP22 mRNA and protein expression levels in the patient and cell‑line samples were evaluated using quantitative polymerase chain reaction and western blotting analyses. Subsequently, stable USP22 gene silencing in cells was achieved using lentiviral-delivered small interfering RNA (siRNA), and an MTT assay was used to evaluate tumor cell proliferation. Expression levels of cell cycle-associated proteins following USP22 knockdown were assessed using western blot analysis. The results revealed that USP22 was upregulated in pharyngeal squamous cell carcinoma. USP22 knockdown, using lentivirus‑delivered siRNA, increased the expression levels of cell cycle proteins P21 and P27, but reduced the levels of phosphorylated retinoblastoma protein, resulting in the inhibition of FaDu cell growth and proliferation. In conclusion, USP22 is involved in the carcinogenesis of human pharyngeal squamous cell carcinoma through regulating tumor cell growth and proliferation.