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1.
  • Mondal, Tanmoy, 1981, et al. (författare)
  • MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA–DNA triplex formation. We have found that RNA–DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.
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2.
  • Runow Stark, Christina, et al. (författare)
  • Brush Biopsy For HR-HPV Detection With FTA Card And AI For Cytology Analysis - A Viable Non-invasive Alternative
  • 2018
  • Ingår i: EAOM2018.
  • Konferensbidrag (refereegranskat)abstract
    • Introduction: Oral cancer accounts for about 800-1,000 new cases each year in Sweden and the ratio of cancer related to high-risk human papillomavirus (HR-HPV) is increasing in the younger population due to changes in sexual habits. The most two frequent HR-HPV types 16 and 18 have both significant oncogenic potential.Objectives: In this pilot study we evaluate two non-invasive automated methods; 1) detection of HR-HPV using FTA cards, and 2) image scanning of cytology for detection of premalignant lesions as well as eradicate the early stage of neoplasia.Material and Methods: 160 patients with verified HR-HPV oropharyngeal cancer, previous ano-genital HR-HPV-infection or potentially malignant oral disorder were recruited for non-invasive brush sampling and analyzed with two validated automated methods both used in cervix cancer screening. For analysis of HR-HPV DNA the indicating FTA elute micro cardTM were used for dry collection, transportation and storage of the brush samples. For analysis of cell morphology changes an automated liquid base Cytology method (Preserve Cyt) combined with deep learning computer aided technique was used.Results: Preliminary results show that the FTA-method is reliable and indicates that healthy and malignant brush samples can be separated by image analysis. Conclusions: With further development of these fully automated methods, it is possible to implement a National Screening Program of the oral mucosa, and thereby select patients for further investigation in order to find lesions with potential malignancy in an early stage. 
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