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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.
Background:
Long noncoding RNA taurine upregulated 1 (TUG1) has been reported to play an important role in human cancers. However, little is known about the role of TUG1 in drug resistance and its mechanism in tongue squamous cell carcinoma (TSCC).
Methods:
Twenty-one cisplatin-sensitive or resistant TSCC patients were enrolled in this study. Cisplatin-resistant cells (SCC25/CDDP and CAL27/CDDP) were used for experiments in vitro. Transfection was performed using Lipofectamine 2000 transfection reagent. The levels of TUG1, microRNA-133b (miR-133b) and cysteine-X-cysteine chemokine receptor 4 (CXCR4) were measured by quantitative real-time polymerase chain reaction or western blot. The cisplatin resistance was investigated by cell viability, transwell invasion and apoptosis assays. The interactions among TUG1, miR-133b and CXCR4 were evaluated by luciferase reporter assay and RNA immunoprecipitation. Murine xenograft model was established using the stably transfected CAL27/CDDP cells.
Results:
TUG1 expression was elevated in cisplatin-resistant TSCC tissues and cells compared with that in sensitive group and its knockdown inhibited cisplatin resistance to SCC25/CDDP and CAL27/CDDP cells. miR-133b was targeted via TUG1 and its overexpression suppressed cisplatin resistance. Moreover, CXCR4 was a target of miR-133b. CXCR4 silence repressed cisplatin resistance, which was reversed by miR-133b knockdown. The level of CXCR4 protein was decreased by inhibition of TUG1 and recuperated by miR-133b knockdown. Besides, interference of TUG1 attenuated tumor growth by regulating miR-133b and CXCR4 in vivo.
Conclusion:
Downregulation of TUG1 impeded cisplatin resistance in TSCC-resistant cells by mediating miR-133b and CXCR4, indicating TUG1 as a promising target for TSCC chemotherapy.
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.

