UCHL1 promotes proliferation and metastasis in head and neck squamous cell carcinoma and could be a potential therapeutic target

Oral Surg Oral Med Oral Pathol Oral Radiol. 2022 Jun;133(6):684-697. doi: 10.1016/j.oooo.2021.11.004. Epub 2021 Nov 18.

Abstract

Objective: The purpose of this study was to research the physiological roles of ubiquitin carboxyl-terminal esterase L1 (UCHL1) in head and neck squamous cell carcinoma (HNSCC).

Study design: Ten HNSCC samples and matched normal oral mucosal tissues were collected. UCHL1 expression of these tissues was detected by the immunohistochemical staining and real-time quantitative polymerase chain reaction. The human HNSCC cell line HN6 UCHL1 knockout (UCHL1 KO) cell line was constructed using CRISPR/CAS9 gene editing and verified by western blotting. Wound healing assay, cell proliferation assay, cell invasion assay, and flow cytometric analysis of the cell cycle and apoptosis were applied to research the role of UCHL1 in HNSCC. Also, an RNAseq gene expression data set and HNSCC patient survival data from The Cancer Genome Atlas were analyzed.

Results: UCHL1 was highly expressed in HNSCC tissues compared with normal oral mucosal tissues (P = .032). A decreased proliferation (P < .0001), migration (P < .0001), and invasion (P = .0049) ability of HN6 cells was exhibited after knockout of UCHL1. However, HN6 UCHL1 KO cells showed no significant differences in the cell cycle or apoptosis. The progression, nodal metastasis status, and stage of HNSCC had a positive correlation with the expression of UCHL1.

Conclusions: UCHL1 plays an important role in HNSCC, and we consider that targeting UCHL1 may be a feasible therapeutic strategy for HNSCC.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Head and Neck Neoplasms* / enzymology
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Squamous Cell Carcinoma of Head and Neck* / enzymology
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Ubiquitin Thiolesterase* / genetics
  • Ubiquitin Thiolesterase* / metabolism

Substances

  • UCHL1 protein, human
  • Ubiquitin Thiolesterase