dc.date.accessioned | 2013-03-12T08:40:36Z | |
dc.date.available | 2013-03-12T08:40:36Z | |
dc.date.issued | 2012 | en_US |
dc.date.submitted | 2012-09-10 | en_US |
dc.identifier.citation | Serguienko, Anastassia. TARGETING OF CANCER STEM CELLS BY LET-7 miRNA. Masteroppgave, University of Oslo, 2012 | en_US |
dc.identifier.uri | http://hdl.handle.net/10852/11486 | |
dc.description.abstract | miRNAs are short non-coding RNA that regulate gene expression at the post-transcriptional level by inhibiting the translation of mRNAs through pairing to their 3’ UTR. The let-7 family of miRNAs regulates cell differentiation during embryogenesis and is responsible for the maintenance of the differentiated state in adult cells. Let-7 miRNA levels are often reduced in malignant tumors and its ectopic expression in cancer cells causes cell growth arrest, reduces invasiveness and down-regulates several oncogenes. To gain a further understanding of their biological functions, the breast cancer cell line MDA-MB-231 was transfected with let-7 miRNA mimics and their effect was examined by qPCR, western blot, flow cytometry and functional assays to determine stem cell characteristics and differentiation. We confirmed that let-7 miRNA mimics reduced cell proliferation, and HMGA2, Cyclin D1, Ras and Lin28A protein level in MDA-MB-231 cells. We found that let-7 miRNA down-regulated the levels of active β-catenin (ABC). We showed for the first time that let-7 miRNAs coordinately induce the enzymes in the serine biosynthesis pathway at the transcriptional level in MDA-MB-231 cells. Furthermore, we found that the protein level of the enzymes is differentially regulated: whereas the first two enzymes of the pathway are up-regulated, the last enzyme, phosphoserine phosphatase (PSPH), is down-regulated.
ABC down-regulation by let-7 mimics is consistent with the tumor suppressor role of let-7 miRNA family and represents an additional mechanism by which let-7 interferes with Wnt pathway.
The regulation of serine biosynthesis pathway is a novel and unexpected function of let-7 that raises many questions and leads to the exciting emerging field: Metaboloepigenetics. | eng |
dc.language.iso | eng | en_US |
dc.title | TARGETING OF CANCER STEM CELLS BY LET-7 miRNA | en_US |
dc.type | Master thesis | en_US |
dc.date.updated | 2012-11-08 | en_US |
dc.creator.author | Serguienko, Anastassia | en_US |
dc.subject.nsi | VDP::473 | en_US |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Serguienko, Anastassia&rft.title=TARGETING OF CANCER STEM CELLS BY LET-7 miRNA&rft.inst=University of Oslo&rft.date=2012&rft.degree=Masteroppgave | en_US |
dc.identifier.urn | URN:NBN:no-32466 | en_US |
dc.type.document | Masteroppgave | en_US |
dc.identifier.duo | 168859 | en_US |
dc.identifier.bibsys | 123517745 | en_US |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/11486/1/Masterxthesis.pdf | |