TUG1/miR-133b/CXCR4 axis regulates cisplatin resistance in human tongue squamous cell carcinoma

Ke Zhang1, Hong Zhou1, Bo Yan1

  • 1The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450000 Henan China.

Abstract

Insights

Long noncoding RNA taurine upregulated 1 (TUG1) impedes cisplatin resistance in tongue squamous cell carcinoma (TSCC) by regulating microRNA-133b (miR-133b) and CXCR4. Downregulating TUG1 shows promise for improving TSCC chemotherapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNA taurine upregulated 1 (TUG1) is implicated in human cancers.
  • The specific role and mechanism of TUG1 in tongue squamous cell carcinoma (TSCC) drug resistance remain largely unknown.

Purpose of the Study:

  • To investigate the role of TUG1 in cisplatin resistance in TSCC.
  • To elucidate the underlying molecular mechanisms involving microRNA-133b (miR-133b) and CXCR4.

Main Methods:

  • Quantitative real-time PCR and western blot to measure TUG1, miR-133b, and CXCR4 levels.
  • In vitro assays (cell viability, invasion, apoptosis) and in vivo murine xenograft models were used to assess cisplatin resistance.
  • Luciferase reporter and RNA immunoprecipitation assays were employed to determine molecular interactions.

Main Results:

  • TUG1 expression was significantly higher in cisplatin-resistant TSCC tissues and cells.
  • TUG1 knockdown reduced cisplatin resistance, while miR-133b overexpression suppressed it.
  • TUG1 targets miR-133b, which in turn targets CXCR4; CXCR4 knockdown repressed resistance, but this effect was reversed by miR-133b inhibition. TUG1 downregulation reduced CXCR4 levels and tumor growth in vivo.

Conclusions:

  • TUG1 downregulation inhibits cisplatin resistance in TSCC by modulating the miR-133b/CXCR4 axis.
  • TUG1 represents a potential therapeutic target for enhancing chemotherapy efficacy in TSCC.