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

Mingyan Xu1,2, Junling Zhang3, Xuemei Lu3

  • 1Department of Implantology, Stomatological Hospital of Xiamen Medical College & Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen 361008, China.

International Journal of Molecular Sciences
|March 11, 2023
PubMed

Insights

SMARCA4, a key component of chromatin remodeling, is upregulated in oral squamous cell carcinoma (OSCC). Its elevated expression promotes OSCC cell invasion and metastasis via epithelial-mesenchymal transition (EMT).

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The role of SMARCA4 (BRG1), an ATPase subunit of the SWI/SNF chromatin remodeling complex, in oral squamous cell carcinoma (OSCC) pathogenesis is not well understood.
  • SMARCA4 is implicated in various cancer development processes, but its specific function in OSCC requires elucidation.

Purpose of the Study:

  • To investigate the biological function and underlying mechanism of SMARCA4 in oral squamous cell carcinoma (OSCC).
  • To explore the relationship between SMARCA4, microRNA miR-199a-5p, and epithelial-mesenchymal transition (EMT) in OSCC.

Main Methods:

  • Tissue microarray analysis to assess SMARCA4 expression in OSCC tissues.
  • In vitro and in vivo experiments to evaluate the effects of SMARCA4 on OSCC cell migration, invasion, and tumor growth.
  • Bioinformatic analysis and luciferase reporter assays to confirm the regulatory relationship between miR-199a-5p and SMARCA4.
  • Mechanistic studies to elucidate the role of the miR-199a-5p-SMARCA4 axis in EMT.

Main Results:

  • SMARCA4 expression is significantly upregulated in OSCC tissues.
  • Increased SMARCA4 expression enhances OSCC cell migration, invasion, and tumor growth in vitro and in vivo.
  • SMARCA4 upregulation is associated with the promotion of epithelial-mesenchymal transition (EMT).
  • SMARCA4 was confirmed as a target gene of microRNA miR-199a-5p.
  • The miR-199a-5p-regulated SMARCA4 promotes tumor cell invasion and metastasis through EMT.

Conclusions:

  • The miR-199a-5p-SMARCA4 axis plays a critical role in OSCC tumorigenesis.
  • This axis promotes OSCC cell invasion and metastasis by regulating epithelial-mesenchymal transition (EMT).
  • Understanding this mechanism offers potential therapeutic strategies for OSCC.
Keywords:
EMTSMARCA4miR-199a-5poral squamous cell carcinoma

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