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| Content Provider | PubMed Central |
|---|---|
| Author | Sharma, Sweta Mandal, Paramita Sadhukhan, Tamal Chowdhury, Rahul Roy Mondal, Nidhu Ranjan Chakravarty, Biman Chatterjee, Tanmay Roy, Sudipta Sengupta, Sharmila |
| Copyright Year | 2015 |
| Abstract | Human Papillomavirus (HPV) type 16 oncoprotein E7 plays a major role in cervical carcinogenesis by interacting with and functionally inactivating various host regulatory molecules. Long noncoding RNA (lncRNA) HOTAIR is one such regulator that recruits chromatin remodelling complex PRC2, creating gene silencing H3K27 me3 marks. Hence, we hypothesized that HOTAIR could be a potential target of E7, in HPV16 related cervical cancers (CaCx). We identified significant linear trend of progressive HOTAIR down-regulation through HPV negative controls, HPV16 positive non-malignants and CaCx samples. Majority of CaCx cases portrayed HOTAIR down-regulation in comparison to HPV negative controls, with corresponding up-regulation of HOTAIR target, HOXD10, and enrichment of cancer related pathways. However, a small subset had significantly higher HOTAIR expression, concomitant with high E7 expression and enrichment of metastatic pathways. Expression of HOTAIR and PRC2-complex members (EZH2 and SUZ12), showed significant positive correlation with E7 expression in CaCx cases and E7 transfected C33A cell line, suggestive of interplay between E7 and HOTAIR. Functional inactivation of HOTAIR by direct interaction with E7 could also be predicted by in silico analysis and confirmed by RNA-Immunoprecipitation. Our study depicts one of the causal mechanisms of cervical carcinogenesis by HPV16 E7, through modulation of HOTAIR expression and function. |
| Related Links | http://dx.doi.org/10.1038/srep11724 |
| Starting Page | 11724 |
| File Format | |
| ISSN | 20452322 |
| e-ISSN | 20452322 |
| Journal | Scientific Reports |
| Volume Number | 5 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2015-07-01 |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Science and technology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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