title: Bridging Links between Long Noncoding RNA HOTAIR and HPV Oncoprotein E7 in Cervical Cancer Pathogenesis.
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.
authors.affiliation: National Institute of Biomedical Genomics, Netaji Subhas Sanatorium, 2nd Floor, P.O. N.S.S, Kalyani 741251, West Bengal, India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Sharma
authors.affiliation: National Institute of Biomedical Genomics, Netaji Subhas Sanatorium, 2nd Floor, P.O. N.S.S, Kalyani 741251, West Bengal, India.
authors.forename: Paramita
authors.initials: P
authors.lastname: Mandal
authors.affiliation: National Institute of Biomedical Genomics, Netaji Subhas Sanatorium, 2nd Floor, P.O. N.S.S, Kalyani 741251, West Bengal, India.
authors.forename: Tamal
authors.initials: T
authors.lastname: Sadhukhan
authors.affiliation: Department of Gynecology, Saroj Gupta Cancer Centre and Research Institute, Kolkata,India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Roy Chowdhury
authors.affiliation: Department of Gynecology, Saroj Gupta Cancer Centre and Research Institute, Kolkata,India.
authors.forename: Nidhu
authors.initials: N
authors.lastname: Ranjan Mondal
authors.affiliation: Department of Gynecology, Saroj Gupta Cancer Centre and Research Institute, Kolkata,India.
authors.forename: Biman
authors.initials: B
authors.lastname: Chakravarty
authors.affiliation: Department of Gynecology, Saroj Gupta Cancer Centre and Research Institute, Kolkata,India.
authors.forename: Tanmay
authors.initials: T
authors.lastname: Chatterjee
authors.affiliation: Sri Aurobindo Seva Kendra, 1H, Gariahat Road (S) Jodhpur Park, Kolkata-700068, West Bengal, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Roy
authors.affiliation: National Institute of Biomedical Genomics, Netaji Subhas Sanatorium, 2nd Floor, P.O. N.S.S, Kalyani 741251, West Bengal, India.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: C561566:HOTAIR long untranslated RNA, human; D006657:Histones; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D050725:Papillomavirus E7 Proteins; D062085:RNA, Long Noncoding; C430461:SUZ12 protein, human; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; C072064:HOXD10 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2