(2015-2017) – Principal Investigator Anca Botezatu, PhD.

Aim: HPV 16 E6/E7 oncogene silencing in SiHa cell culture (as experimental model);     Detection of MBD2, MBD3 genome wide DNA binding pattern (e.g. promoters, gene control region, transcriptional enhancers, etc.) in untreated and siRNA treated SiHa cell culture; Comparative study between the MBD2 and MBD3 genome wide DNA binding pattern; Cellular targets data integration in viral infection context.

Partners: Coordinator:– „Stefan S. Nicolau” Institute of Virology,  project director Anca Botezatu, PhD

Working team: Botezatu A, Plesa A, Iancu I,

Funding: IVN=550 000 LEI

Project: UEFISCDI – Research projects to stimulate the establishment of young independent research teams – TE,PN-II-RU-TE-2014-4-2502
Implementation period: October 2015 – September 2017

Summary: Cervical cancer is the third most commonly diagnosed type of cancer and one of the most frequently occurring malignant tumors in women worldwide. Human papilloma virus (HPV) is considered the etiologic agent of cervical neoplasia. The transforming potential of high risk human papillomavirus (hrHPV) is due to E6 and E7 viral oncoproteins. Persistent hrHPV infection leads to changes in the host genome and epigenome. The control of gene expression is complex and involves epigenetic changes (DNA methylation, histone modification, miRNAs activity). The nucleosome remodeling and deacetylation complex (NuRD) is a group of associated proteins with ATP-dependent chromatin remodeling and histone deacetylase activities. MBD2 and MBD3 proteins from NuRD complex exhibit methyl-CpG-binding domains (MBD), which mediate an interaction with methylated DNA. At molecular level, MBD2 binds to methylated DNA (at 5-methylcytosine -5 mC), while MBD3 binds to DNA at 5-hydroxymethylcytosine (5 hmC). Given the increasing data regarding the MBD2 and MBD3 functional differences and similarities, the proposal aims to assess the viral oncogenes influence on the MBDs overall binding pattern to CpG islands from promoters, gene control region, enhancers, gene bodies. The resulting data will help to elucidate the mechanisms leading to oncogenesis and to identify new potential therapeutic targets

Results:

1. Iulia V Iancu, Gabriela Anton, Anca Botezatu, Irina Huică, Anca Nastase, Demetra Socolov, Anca Stanescu, Olimpia Dima, Nicolae Bacalbasa, Adriana Pleşa. LINC01101 and LINC00277 expression levels as novel factors in HPV‐induced cervical neoplasia.  Journal of cellular and molecular medicine. J Cell Mol Med. 2017; 21(12):3787-3794. doi: 10.1111/jcmm.13288.
2. Adriana Pleșa, Anca Botezatu, Iulia V Iancu, Ioana Pitica, Demetra Socolov, Gabriela Anton. MOZ/MORF complex components expression levels in HPV-cervical cancer. 42nd FEBS Congress “From molecules to cells and back”, 2017, Jerusalem, Israel, abstract în The FEBS Journal, 2017, 284 (Suppl. 1), P.3.2-024, pg 225, ISSN: 1742-464X eISSN:1742-4658. IF= 5.622.
3. Anca Botezatu, Iulia V Iancu, Adriana Pleșa, Demetra Socolov, Gabriela Anton. The effect of hrHPV infection on DNA methylation process during cervical oncogenesis. 42nd FEBS Congress “From molecules to cells and back”, 2017, Jerusalem, Israel, abstract în The FEBS Journal 2017, 284 (Suppl. 1), P.3.2-014, pg 222, ISSN: 1742-464X eISSN:1742-4658. IF= 5.622.
4. Iulia V Iancu, Anca Botezatu, Adriana Pleșa, Demetra Socolov, Gabriela Anton. Long non-coding RNAs expression pattern in cervical oncogenesis. 42nd FEBS Congress “From molecules to cells and back”, 2017, Jerusalem, Israel, abstract în The FEBS Journal, 2017, 284 (Suppl.1), P.3.2-013, pg 222, ISSN: 1742-464X eISSN:1742-4658. IF= 5.622.
5. Anca Botezatu, Iulia V Iancu, Irina Huică, Adriana Pleșa, Gabriela Anton. Epigenomic approaches in cancer pathology. The 10th National Pathology Symposium, cu participare internațională, 2017, București, 23-25 noiembrie.
6. Anca Botezatu, Iulia Iancu, Adriana Pleşa, Socolov Socolov, Gabriela Anton. The levels of DNA methyltransferases and MBD genes expression in HPV-induced cervical lesions. Epigenetics & chromatin meetings and courses, 2016, Cold Spring Harbour Laboratory, New York, USA, abstract in Epigenetics & chromatin meetings, 2016, p 35
7. Iulia Iancu, Anca Botezatu, Adriana Pleşa, Demetra Socolov, Gabriela Anton. Expression levels of PRC2 members in HPV-induced cervical lesions. Epigenetics & chromatin meetings and courses, 2016, Cold Spring Harbour Laboratory, New York, USA, abstract in Epigenetics & chromatin, 2016, p 114.
8. Iulia Virginia Iancu, Anca Botezatu, Adriana Pleşa, Irina Huică, Demetra Socolov, Gabriela Anton. H19 and MALAT1 lncRNAs expression levels as prognostics factors in cervical oncogenesis. Congresul ISGE “17th World Congress of Gynecological Endocrinology”. 2016, Florenţa, Italia, in Gynecological Endocrinology, 32 (Sup1)  p 113, P-83. ISSN:0951-3590 eISSN:1473-0766. IF=2.277
9. Iulia Iancu, Anca Botezatu, Adriana Plesa, Irina Huica, Demetre Socolov, Gabriela Anton. Analiza expresiei unor histon-demetilaze ca reglatori epigenetici in leziuni displazice de col uterin HPV-induse. Sesiunea Stiintifica anuala a institutului „Victor Babes” si al-8-lea Simpozion National de Patologie. „Medicina de precizie – de la modele experimentale la biomarkeri”, 19-21 noiembrie 2015, Bucuresti . Abstract aparut in Volum de rezumate, 2015, pg56