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

Abstract

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.

Poorly Differentiated Neuroendocrine Larynx Carcinoma: Clinical Features and miRNAs Signature—A New Goal for Early Diagnosis and Therapy?

“…In fact, miR-133 upregulation increases the cisplatin chemosensitivity of cisplatinresistant non small cell lung cancer (NSCLC) cells. Together with TUG1 and CRC4, it is involved in cisplatin resistance even in tongue squamous carcinoma patients [21,22]. Similarly, the findings herein reported, suggest a possible onsuppressive role for miR-133b due to its prominent downregulation in LNEC tissues.…”

LncRNA TUG1 promotes Ewing's sarcoma cell proliferation, migration, and invasion via the miR-199a-3p-MSI2 signaling pathway

“…Wang et al reported that TUG1 facilitated the proliferation, migration and invasion of hepatocellular carcinoma cells through up-regulation of COL1A1 via sequestering miR-29c-3p [40]. A study by Zhang et al showed that depletion of TUG1 abated cisplatin resistance of to ngue squamous cell carcinoma cells via targeting miR-133b/CXCR4 axis [41]. In this study, a negative correlation between TUG1/MSI2 and miR-199a-3p in Ewing's sarcoma patient samples was observed.…”

lncRNA RPSAP52 induced the development of tongue squamous cell carcinomas via miR‐423‐5p/MYBL2

“…Growing lncRNAs have been noted to involve in the initiation and development of several tumours including TSCC. For instance, Zhang et al 35 indicated that TUG1 level was overexpressed in TSCC cells and tissues of cisplatin resistance. Knockdown of TUG1 suppressed cisplatin resistance to CAL27/CDDP and SCC25/CDDP cells via modulating CXCR4 and miR‐133b.…”