During his PhD studies, Karim Rahimi researched the possibility of murine microRNAs miR-302 host RNA as a stem cell marker.

MicroRNAs are short, non-coding RNAs that regulate gene expression and are involved in many biological processes. The miR-302s/367 gene encodes a collection miRNA that is expressed under the control of stem cell specific factors such as Oct4, Sox2 and Nanog. MiR-302 can induce somatic cells to become pluripotent and suppress mRNAs which are required for differentiation.
Stem cells have certain unique characteristics in common with cancer stem cells, including that they are multipotent and their ability for self-renewal.
In the present study, we examined the possibility of using the miR-302-regulatory sequences to drive stem cell specific expression of reporter genes. Expression of reporters in embryonic stem cells under the control of a 2.1 kb upstream region was less than expected. When using a luciferase promoter test assay this could be explained by the presence of a repressor element, which ranged from 600 bp and 850 bp upstream of the start site of transcription. Irrespective of the length of the regulatory sequences, we observed a strong down-regulation of EGFP reporter in mice and in tumors in relation to embryonic stem cells, though the transcript could be measured by PCR. By use of the neomycin phosphotransferase (neo) as a reporter, however, we were able to select cells from teratomas, which we have used as tumor models for the validation of the method principle. As our hypothesis predicted was the expression of miR-302 promoter-driven reporter depending on that the cells were undifferentiated and cells without selection rapidly lost their stem cell characteristics.

The new research findings contribute to the understanding of how one can use a non-coding RNA as a host for reporter gene expression and how to select cancer stem cells from tumors using a selection marker gene driven by a stem cell specific promoter.

The PhD degree was completed at the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

This résumé is prepared by the PhD student.

Time: Wednesday 24 February 2016 at 12.00
Place: Building 1131, room 623, Department of Molecular Biology and Genetics, Aarhus University, C.F. Møller Allé 3, 8000 Aarhus C
Title of dissertation: Analysis of miR-302 host RNA as a stem cell marker
Contact information: Karim Rahimi, e-mail: karim@mbg.au.dk, tel.: +45 8715 4952
Members of the assessment committee:
Professor Branko Zevnik, In vivo Research Facility (ivRF), CECAD - Excellent in Aging Re-search, University of Cologne, Germany
Professor Jan Mollenhauer, Molecular Oncology Group, Institute of Molecular Medicine, University of Southern Denmark
Professor Claus Oxvig (chair), Department of Molecular Biology and Genetics, Aarhus University, Denmark
Main supervisor:
Associate Professor Ernst-Martin Füchtbauer, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University, Denmark
Co-supervisors: 
Associate Professor Seyed Javad Mowla, Department of Molecular Genetics, Tarbiat Modares University, Tehran-Iran
Professor Fardin Fathi, Cellular-Molecular research center, Kurdistan University of Medical Science, Sanandaj-Iran
Language: The PhD dissertation will be defended in English.

The defense is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, room 128-134, 8000 Aarhus C.