The Laryngoscope · 2018 · 12 citations · 37 references
MedicineCell BiologyOncologyMetastasisMolecular OncologySignal TransductionCancer Cell SignalingCancer ProgressionLaryngeal CancerMalignant NeoplasmsOncogenic Signaling PathwaysSquamous Cell CarcinomaCancer Signaling PathwaysCell Migration AssaysGene Knockdown MechanismsLaryngeal Squamous Cell CarcinomaProtein Expression LevelsTumor Growth DynamicsTumor Growth RateWestern Blot Analysis
OBJECTIVES/HYPOTHESIS: Transformer-2 protein homolog beta (Tra2β) generally plays an important role in various human cancers, but its role and the underlying mechanisms in laryngeal squamous cell carcinoma (LSCC) remained unknown. So this study aimed to assess the clinical significance and regulatory mechanisms of Tra2β in LSCC. STUDY DESIGN: Laboratory analysis. METHODS: Expression of Tra2β was compared in human LSCC tissue samples and paired adjacent normal tissue samples. The in vitro effects of Tra2β expression in Hep-2 cells on their proliferation, invasion, and migration were assessed by CCK-8 assays, Matrigel invasion, and transwell migration assays. In addition, the effects of downregulation of Tra2β on the activation of PI3K/AKT signaling pathway were measured using Western blot analysis. The effect of Tra2β on the growth of tumors was detected in the Hep-2-injected xenograft models in vivo. RESULTS: Reverse-transcription quantitative polymerase chain reaction analysis and immunochemistry analysis indicated that the increased expression of Tra2β in LSCC was significantly associated with poor differentiation, lymph node metastasis, and advanced clinical stage. In vitro knockdown of Tra2β caused a significant decrease in the proliferation, invasion, and migration of Hep-2 cells. Tra2β silencing decreased the expression of Bcl-2 but increased Bax and Caspase-3 both in mRNA and protein levels. Furthermore, knockdown of Tra2β eliminated the suppressive effects of activation of PI3K/AKT signaling. In vivo knockdown of Tra2β significantly inhibited the tumor growth of Hep-2-injected xenograft mice. CONCLUSIONS: The results of the present study demonstrated that knockdown of Tra2β inhibits the proliferation and invasion of LSCC cells, at least partly via inhibiting PI3K/AKT signaling. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E318-E328, 2019.
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