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miR-204 enhances p27 mRNA stability by targeting Brd4 in head and neck squamous cell carcinoma

Caihua Wang1, Yonghong Zhang1, Dayong Zhou2

  • 1Department of Ear, Nose and Throat, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China.

Oncology Letters
|September 26, 2018
PubMed

Insights

MicroRNA-204 (miR-204) acts as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC). It enhances p27 mRNA stability by targeting Brd4, inhibiting cancer cell proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with complex molecular underpinnings.
  • MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
  • The specific role of miR-204 in HNSCC and its regulatory mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the function of microRNA-204 (miR-204) in head and neck squamous cell carcinoma (HNSCC).
  • To explore the mechanism by which miR-204 modulates the stability of cyclin-dependent kinase inhibitor 1B (p27) mRNA.
  • To identify potential molecular targets of miR-204 in HNSCC.

Main Methods:

  • Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were employed to quantify miR-204 and Brd4 expression.
  • Cell viability, cell cycle, and apoptosis assays were performed to assess the functional impact of miR-204.
  • Luciferase reporter assays and mRNA stability assays were utilized to elucidate the underlying molecular mechanisms.

Main Results:

  • miR-204 expression was found to be significantly downregulated in HNSCC tissues compared to adjacent normal tissues.
  • A negative correlation was observed between the expression levels of miR-204 and bromodomain-containing protein 4 (Brd4) in HNSCC.
  • Overexpression of miR-204 inhibited HNSCC cell proliferation, induced G1/S phase cell cycle arrest, and promoted apoptosis.
  • miR-204 was identified as a direct target of Brd4, and its upregulation enhanced p27 mRNA stability.
  • Co-expression of Brd4 with miR-204 mimics partially reversed the inhibitory effects of miR-204 on proliferation and p27 mRNA stability.

Conclusions:

  • miR-204 functions as a tumor suppressor in HNSCC.
  • miR-204 enhances p27 mRNA stability, thereby inhibiting HNSCC cell proliferation.
  • The tumor-suppressive role of miR-204 is mediated through its targeting of Brd4 in HNSCC.
Keywords:
bromodomain-containing protein 4cyclin-dependent kinase inhibitor 1Bhead and neck squamous cell carcinomamicroRNA-204

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