Abstract
Emerging evidence suggests that Nanog is involved in cervical tumorigenesis. However, the regulating role of Nanog in tumorigenesis and chemosensitivity are still poorly understood. In this study, Nanog was disrupted by transcription activator-like effector nucleases (TALEN) in Hela cells and its expression was significantly decreased in a single-cell derived sub-clone with biallelic mutations. The disruption of Nanog not only induced down regulation of some other core transcription factor genes for cell self-renewal, such as Oct4, Sox2 and FoxD3, but also led to the down regulation of some mesenchymal representative genes, vimentin and N-adherin, and up regulation of the epithelial gene, E-cadherin. In addition, the invasiveness and clonogenicity of the Hela cells were obviously affected, and surprisingly their sensitivities to anti-cancer drugs were also significantly increased in vitro. After Xenograft into nude mice, the growth volumes of the neoplasms from the Nanog disrupted Hela cells were significantly smaller compared with those from wild type ones. In conclusion, these results suggest that disruption of Nanog may reverse the status of epithelial-mesenchymal transition, which is critical in tumorigenesis, and alleviate chemoresistance, as well as their invasiveness, in cervical cancer cells.
Highlights
The cervical cancers are the third most common cancers in females, with their mortality in the fourth place [1]
Nanog was disrupted by transcription activatorlike effector nucleases (TALEN) and that seemed to result in a dramatic reversal of epithelial-mesenchymal transition (EMT) process in Hela cells
The decrease of E-cadherin expression is a critical step in the process of EMT [18], and it is often companied with increase of N-cadherin expression
Summary
The cervical cancers are the third most common cancers in females, with their mortality in the fourth place [1]. The correlation between Nanog expression and the cervical cancer remains unclear and the molecular mechanisms of Nanog in inducing EMT, metastasis and chemoresistance need to be further clarified. Since their discoveries, various kinds of RNAi techniques have been widely used to repress some gene expression in vitro because of their convenience in use. Nanog of Hela cells was biallelicly disrupted by TALEN in order to investigate if it plays any role in affecting invasiveness, EMT and chemoresistance in human cervical cancers. The mice implanted with Nanog disrupted Hela cells lived longer than those with wild type ones (6-8 weeks vs. 4-5 weeks) (Figure 7)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
