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TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas

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机构: [1]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [2]Department of Head and Neck Surgery of Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China. [3]Division of Radiation and Cancer Biology, Department of Radiation Oncology, Washington University in Saint Louis, School of Medicine, 4511 Forest Park, St. Louis, MO 63108, USA.
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关键词: TCAB1 Head and neck cancers Proliferation Invasion Biomarker

摘要:
Background: WRAP53, including alpha, beta and gamma isoforms, plays an important role not only in the stability of p53 mRNA, but also in the assembly and trafficking of the telomerase holoenzyme. It has been considered an oncogene and is thought to promote the survival of cancer cells. The aim of this study was to detect the role of TCAB1 ( except WRAP53 alpha) in the occurrence and development of head and neck carcinomas. Methods: Immunohistochemistry was used to detect the TCAB1 expression in clinical specimen sections and performed western blotting to check the TCAB1 expression levels in cell lines. TCAB1 was depleted using shRNA lentivirus and the knockdown efficiency was assessed using q-PCR and Western blotting. We performed CCK-8 assays and flow cytometry to check the cell proliferation potential and used the trans-well assay to test the invasion ability in vitro. Xenografts were used to detect the tumor formation potential in vivo. Moreover, we performed cDNA microarray to investigate the candidate factors involved in this process. Results: We observed a notable overexpression of TCAB1 in head and neck carcinoma clinical specimens as well as in carcinoma cell lines. Knockdown of TCAB1 decreased the cellular proliferation potential and invasion ability in vitro. cDNA microarray analysis suggested the possible involvement of several pathways and factors associated with tumorigenesis and carcinoma development in the TCAB1-mediated regulation of cancers. Furthermore, the xenograft assay confirmed that the depletion of TCAB1 would inhibit tumor formation in nude mice. The immunohistochemistry results of the mice tumor tissue sections revealed that the cells in shTCAB1 xenografts showed decreased proliferation potential and increased apoptotic trend, meanwhile, the angiogenesis was inhibited in the smaller tumors form shTCAB1 cells. Conclusions: Our study demonstrated that depletion of TCAB1 decreased cellular proliferation and invasion potential both in vitro and in vivo. The data indicated that TCAB1 might facilitate the occurrence and development of head and neck carcinomas. In future, TCAB1 might be useful as a prognostic biomarker or a potential target for the diagnosis and therapy of head and neck carcinomas.

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基金编号: 81321002, 81228017, 30901689, 81172579, and 81170959

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出版当年[2014]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学 3 区 生化与分子生物学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 肿瘤学
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出版当年[2014]版:
Q1 ONCOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
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