Abstract
BackgroundWRAP53, including α, β and γ 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 WRAP53α) in the occurrence and development of head and neck carcinomas.MethodsImmunohistochemistry 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.ResultsWe 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.ConclusionsOur 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.
Highlights
WRAP53, including α, β and γ isoforms, plays an important role in the stability of p53 mRNA, and in the assembly and trafficking of the telomerase holoenzyme
Our findings showed that TCAB1 was overexpressed in human head and neck carcinoma cell lines, including human nasopharyngeal carcinoma (NPC) cell line CNE1, oral squamous carcinoma cell (OSCC) lines HSC-3, Cal-27, and adenoid cystic carcinoma (ACC) cell line ACC2
The results indicated that TCAB1 was significantly overexpressed in NPC cell line CNE1, OSCC cell lines HSC-3 and Cal-27, and in ACC cell line ACC2, while the expression level was relatively low in human primary normal cells, including human periodontal ligament cells (PDLC) and human dental pulp cells (DPC) (Figure 1a, b)
Summary
WRAP53, including α, β and γ isoforms, plays an important role in the stability of p53 mRNA, and 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. Since the localization of telomerase to Cajal body was regarded a crucial step in the telomerase holoenzyme assembly in telomerase positive tumors, mutation of TCAB1 gene could result in disorders as dyskeratosis congenita associated with telomeres shortening, which partly caused aging senescence or cancer [13,14]. It is evident that TCAB1 might be an oncogene which to a certain extend could facilitate tumorigenesis and tumor development
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