PMID- 30597574 OWN - NLM STAT- MEDLINE DCOM- 20191023 LR - 20200108 IS - 1531-4995 (Electronic) IS - 0023-852X (Linking) VI - 129 IP - 9 DP - 2019 Sep TI - Tra2beta silencing suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting PI3K/AKT signaling. PG - E318-E328 LID - 10.1002/lary.27716 [doi] AB - OBJECTIVES/HYPOTHESIS: Transformer-2 protein homolog beta (Tra2beta) 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 Tra2beta in LSCC. STUDY DESIGN: Laboratory analysis. METHODS: Expression of Tra2beta was compared in human LSCC tissue samples and paired adjacent normal tissue samples. The in vitro effects of Tra2beta 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 Tra2beta on the activation of PI3K/AKT signaling pathway were measured using Western blot analysis. The effect of Tra2beta 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 Tra2beta in LSCC was significantly associated with poor differentiation, lymph node metastasis, and advanced clinical stage. In vitro knockdown of Tra2beta caused a significant decrease in the proliferation, invasion, and migration of Hep-2 cells. Tra2beta silencing decreased the expression of Bcl-2 but increased Bax and Caspase-3 both in mRNA and protein levels. Furthermore, knockdown of Tra2beta eliminated the suppressive effects of activation of PI3K/AKT signaling. In vivo knockdown of Tra2beta significantly inhibited the tumor growth of Hep-2-injected xenograft mice. CONCLUSIONS: The results of the present study demonstrated that knockdown of Tra2beta 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. CI - (c) 2018 The American Laryngological, Rhinological and Otological Society, Inc. FAU - Ni, Hao-Sheng AU - Ni HS AUID- ORCID: 0000-0002-8491-6707 AD - Department of Otorhinolaryngology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Otorhinolaryngology, Affiliated Hospital of Nantong University, Nantong, China. FAU - Hu, Song-Qun AU - Hu SQ AD - Department of Otorhinolaryngology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Otorhinolaryngology, Affiliated Hospital of Nantong University, Nantong, China. FAU - Chen, Xi AU - Chen X AD - Department of Otorhinolaryngology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Liu, Yi-Fei AU - Liu YF AD - Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China. FAU - Ni, Ting-Ting AU - Ni TT AD - Department of Oncology, Nantong Tumor Hospital, Nantong, China. FAU - Cheng, Lei AU - Cheng L AD - Department of Otorhinolaryngology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181231 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Nerve Tissue Proteins) RN - 0 (TRA2B protein, human) RN - 170974-22-8 (Serine-Arginine Splicing Factors) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Carcinoma, Squamous Cell/*genetics MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Gene Silencing/*physiology MH - Humans MH - Laryngeal Neoplasms/*genetics MH - Nerve Tissue Proteins/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Serine-Arginine Splicing Factors/*metabolism MH - Signal Transduction/*genetics OTO - NOTNLM OT - Laryngeal squamous cell carcinoma OT - PI3K/AKT signaling pathway OT - cell migration OT - cell proliferation OT - transformer-2 protein homology beta EDAT- 2019/01/01 06:00 MHDA- 2019/10/24 06:00 CRDT- 2019/01/01 06:00 PHST- 2018/10/26 00:00 [accepted] PHST- 2019/01/01 06:00 [pubmed] PHST- 2019/10/24 06:00 [medline] PHST- 2019/01/01 06:00 [entrez] AID - 10.1002/lary.27716 [doi] PST - ppublish SO - Laryngoscope. 2019 Sep;129(9):E318-E328. doi: 10.1002/lary.27716. Epub 2018 Dec 31.