HDAC6 is a prognostic biomarker that mediates IL-13 expression to regulate macrophage polarization through AP-1 in oral squamous cell carcinoma

Sci Rep. 2022 Jun 22;12(1):10513. doi: 10.1038/s41598-022-14052-w.

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide that is characterized by abnormal lesions or malignant hyperplasia of soft and hard tissues in the oral cavity. Previous research has found that HDAC6 may be a potential therapeutic target for cancer patients and has the ability to regulate immune cells. However, the mechanism of HDAC6 in OSCC pathogenesis is unclear. We collected clinical samples and analyzed the level of HDAC6 in OSCC patients. The results showed that in the high HDAC6 expression group, HDAC6 expression was positively correlated with the grade of OSCC (R = 0.182, P = 0.036) and that this group had a 3.248-fold increase in the mortality risk compared with the low HDAC6 expression group (P = 0.003). Survival analysis also identified a correlation between the expression of HDAC6 and overall survival in OSCC patients, and it was found that the expression of HDAC6 was inversely correlated with survival (P ≤ 0.001). In addition, we found that HDAC6 induced IL-13 expression through AP-1, resulting in M2 polarization of macrophages. Together, these results demonstrate that the level of HDAC6 may be a useful prognostic biomarker and offer a novel immune cell-related therapeutic strategy of targeting IL-13 in OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Histone Deacetylase 6* / genetics
  • Histone Deacetylase 6* / metabolism
  • Humans
  • Interleukin-13 / metabolism
  • Macrophage Activation
  • Macrophages* / metabolism
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Transcription Factor AP-1 / metabolism

Substances

  • Biomarkers
  • IL13 protein, human
  • Interleukin-13
  • Transcription Factor AP-1
  • HDAC6 protein, human
  • Histone Deacetylase 6