MiR-199a-5p-Regulated SMARCA4 Promotes Oral Squamous Cell Carcinoma Tumorigenesis

Int J Mol Sci. 2023 Mar 1;24(5):4756. doi: 10.3390/ijms24054756.

Abstract

SWI/SNF related, matrix associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1), an ATPase subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, plays an important regulatory role in many cytogenetic and cytological processes during cancer development. However, the biological function and mechanism of SMARCA4 in oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to investigate the role of SMARCA4 in OSCC and its potential mechanism. Using a tissue microarray, SMARCA4 expression was found to be highly upregulated in OSCC tissues. In addition, SMARCA4 upregulate expression led to increased migration and invasion of OSCC cells in vitro, as well as tumor growth and invasion in vivo. These events were associated with the promotion of epithelial-mesenchymal transition (EMT). Bioinformatic analysis and luciferase reporter assay confirmed that SMARCA4 is a target gene of microRNA miR-199a-5p. Further mechanistic studies showed that the miR-199a-5p regulated SMARCA4 can promote the invasion and metastasis of tumor cells through EMT. These findings indicate that the miR-199a-5p- SMARCA4 axis plays a role in tumorigenesis by promoting OSCC cell invasion and metastasis through EMT regulation. Our findings provide insights into the role of SMARCA4 in OSCC and the mechanism involved, which may have important implications for therapeutic purposes.

Keywords: EMT; SMARCA4; miR-199a-5p; oral squamous cell carcinoma.

MeSH terms

  • Carcinogenesis* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • DNA Helicases* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Mouth Neoplasms* / pathology
  • Nuclear Proteins / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Transcription Factors / metabolism

Substances

  • DNA Helicases
  • MicroRNAs
  • Nuclear Proteins
  • SMARCA4 protein, human
  • Transcription Factors
  • mirn199 microRNA, human