GABA regulates the proliferation and apoptosis of head and neck squamous cell carcinoma cells by promoting the expression of CCND2 and BCL2L1

Life Sci. 2023 Dec 1:334:122191. doi: 10.1016/j.lfs.2023.122191. Epub 2023 Oct 20.

Abstract

Gamma-aminobutyric acid (GABA) is a multifunctional molecule that is widely present in the nervous system and nonneuronal tissues. It plays pivotal roles in neurotransmission, regulation of secretion, cell differentiation, proliferation, and tumorigenesis. However, the exact mechanisms of GABA in head and neck squamous cell carcinomas (HNSCCs) are unknown. We took advantage of RNA sequencing in this work and uncovered the potential gene expression profiles of the GABA-treated HNSCC cell line HN4-2. We found that the expression of CCND2 and BCL2L1 was significantly upregulated. Furthermore, GABA treatment inhibited the cell apoptosis induced by cisplatin and regulated the cell cycle after treatment with cisplatin in HN4-2 cells. Moreover, we also found that GABA could upregulate the expression of CCND2 and BCL2L1 after treatment with cisplatin. Our results not only reveal the potential pro-tumorigenic effect of GABA on HNSCCs but also provide a novel therapeutic target for HNSCC treatment.

Keywords: Apoptosis; BCL2L1; CCND2; GABA; HNSCCs; Proliferation.

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / metabolism
  • Cyclin D2 / genetics
  • Cyclin D2 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • bcl-X Protein / metabolism

Substances

  • Cisplatin
  • CCND2 protein, human
  • Cyclin D2
  • BCL2L1 protein, human
  • bcl-X Protein