Cell cycle (Georgetown, Tex.) · 2020
TRG-AS1 is a potent driver of oncogenicity of tongue squamous cell carcinoma through microRNA-543/Yes-associated protein 1 axis regulation.
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He Shuwei, Wang Xu, Zhang Jingjing, Zhou Fan, Li Lei, Han Xingmin
Аннотация
The long noncoding RNA T cell receptor gamma locus antisense RNA 1 (TRG-AS1) plays an important role in glioblastoma progression. The objective of this study was to determine the expression status of TRG-AS1 in tongue squamous cell carcinoma (TSCC). The regulatory effects of TRG-AS1 depletion on the malignant processes of TSCC cells were illustrated both in vitro and in vivo. Additionally, the precise molecular mechanisms through which TRG-AS promotes TSCC oncogenicity were investigated. TRG-AS1 expression in TSCC tissues and cell lines was detected using reverse transcription-quantitative PCR. Functional experiments including Cell Counting Kit-8 assay, flow cytometric apoptotic assay, migration and invasion assays, and xenograft tumor model analysis were conducted to severally determine the effects of TRG-AS1 on TSCC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. Herein, TRG-AS1 was highly expressed in TSCC and closely associated with advanced TNM stage, high lymph node metastasis, and poor overall survival. Functionally, TRG-AS1 depletion suppressed TSCC cell proliferation, migration, and invasion in vitro; promoted cell apoptosis; and attenuated tumor growth in vivo. Mechanistically, TRG-AS1 served as a molecular sponge for microRNA-543 (miR-543), thereby contributing to the increased expression of Yes-associated protein 1 (YAP1) - a miR-543 target. Rescue experiments confirmed that miR-543 inhibition or YAP1 overexpression abrogated the anticancer effects of TRG-AS1 silencing in TSCC cells. In conclusion, TRG-AS1 aggravates TSCC malignancy by regulating the miR-543/YAP1 axis. Identification of the TRG-AS1/miR-543/YAP1 regulatory pathway may provide novel insights into TSCC diagnosis, prognosis, and therapy.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAnimalsAntineoplastic AgentsBase SequenceCarcinogenesisCarcinoma, Squamous CellCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMice, Inbred BALB CMice, NudeMicroRNAsMiddle AgedModels, BiologicalPhenotypeRNA, Long NoncodingSignal TransductionTongue NeoplasmsTranscription FactorsUp-RegulationYAP-Signaling Proteins