Abstract
Telomerase Cajal body protein 1 (TCAB1), which is involved in Cajal body maintenance, telomere elongation and ribonucleoprotein biogenesis, has been linked to cancer predisposition, including nasopharyngeal carcinoma (NPC), due to its oncogenic properties. However, there are no specific reports to date on the functional relevance of TCAB1 and Epstein–Barr virus (EBV), which is considered to be a risk factor for NPC. In this study, we first examined NPC clinical tissues and found a notable overexpression of TCAB1 in EBV-positive specimens. Secondly, on a cellular level, we also observed that TCAB1 expression rose gradually along with the increased duration of EBV exposure in NPC cell lines. Additionally, EBV infection promoted cell proliferation and telomerase activity, but the activation was significantly inhibited after TCAB1 knockdown. Moreover, depletion of TCAB1 caused both cell cycle arrest and apoptosis, and suppressed the activation of ataxia telangiectasia and Rad3 related protein (ATR) induced by EBV, resulting in accumulation of DNA damage. Taken together, we here demonstrate that up-regulated expression of TCAB1, induced by EBV in the development of NPC, is involved in stimulating telomerase activity and regulating the DNA damage response within the context of EBV infection.
Highlights
The WRAP53 gene, located on chromosome 17p13, encodes three functional products: WRAP53α, -β, and -γ
In spite of the limited number of Epstein–Barr virus (EBV)-negative clinical samples, this finding presumedly alluded to an oncogenic property of Telomerase Cajal body protein 1 (TCAB1) and gave a hint that up-regulation of TCAB1 might be important to the process of EBV infection during Nasopharyngeal carcinoma (NPC) tumourigenesis, prompting us to further investigate the potential association between TCAB1 and EBV at a cellular level
We examined the expression level of TCAB1 in two NPC cells and two control cell lines before and after EBV infection, and elevated TCAB1 expression was found as the duration of EBV infection increased
Summary
The WRAP53 gene, located on chromosome 17p13, encodes three functional products: WRAP53α, -β, and -γ. It is known that EBV infection resulted in DNA damage accumulation and attenuated the following response in NPC, whether TCAB1 that is significantly up-regulated in EBV-positive NPC samples in our study is involved in this process is unclear. To investigate EBV infection in fifty human NPC specimens, we performed immunohistochemistry (IHC) to examine expression of LMP1 and observed a positivity rate of 76% (38 of 50 samples, Fig. 1A,B).
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