MIRNAPROSTATECANCER · MicroRNA in development and progression of prostate cancer
6РП — Действия „Мария Кюри“
- Период
- 2006-10-01 → 2007-09-30
- Финансиране от ЕС
- 40 000 €
- Участници
- 1
- Схема
- ERG
Линиите свързват координатора с партньорите.
Накратко на български
МикроРНК-молекулите, конкретно miR-16, се изследват за влиянието им върху развитието на рака на простатата. Разбирането на връзката между miR-16 и протеина E2F3 помага да се разбере как се контролира деленето и смъртта на раковите клетки.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - MIRNAPROSTATECANCER (MicroRNA in development and progression of prostate cancer)
This project studied the miRNA expression in 27 primary prostate tumours, 5 normal prostates and 9 prostate cell lines by miRNA micro array screening. They gathered results showing that miR-16 is down regulated in prostate cancer. Further, deletion of 13q14, where one of the two the miR-16 encoding gene is located, is frequently deleted in prostate cancer (30-70%); however, no reasonable candidate has yet been identified in this region. The project optimised the in situ hybridisation on prostate formalin fixed paraffin embedded specimens for miR-16 and preliminary observations indicates that miR-16 is expressed in luminal epithelial cells and down regulated in cancerous tissues. They found that inhibitors of miR-16 in Du145 cells increase the proliferation rate by 254% (p=0.0017) in vitro, and when ectopically expressing miR-16 in PC3 cells (with low levels of miR-16) the proliferation rate decreases. In addition, we have also seen an increase of apoptosis when miR-16 is overexpressed in PC3 cells with 128-152% depending on method of analysis. Using in silico analyses miR-16 was predicted to target the transcription factor E2F3 that is involved in cell cycle regulation, and has been shown to induce increased proliferation in prostate cancer cells5. It is also a prostate cancer marker, upregulated in 68% of prostate cancers, and correlated with poor survival. The project confirmed that miR-16 has a regulatory effect on E2F3 in vitro; the E2F3 levels are abolished when ectopically expressing miR-16, and when blocking miR-16 in Du145 the E2F3 levels increase with 240%. The Luciferase assay showed that miR-16 binds to the E2F3 3'utr, and that it is corresponding to increased levels of miR-16. Previously, we have found that the over expression of E2F3 protein in prostate cancer cannot been linked to DNA amplification of the E2F3 encoding gene or mRNA over expression, indicating that the deregulation of E2F3 might be caused by miRNAs. The protein levels of E2F3 in different prostate cell lines show an almost perfect negative correlation to the level of miR-16 detected by qRT-PCR Taqman. Hence, these results nicely ties in with this theory.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
In Europe, around 80 cases of prostate cancer per 100,000 population diagnosed each year. However, very little is known about the molecular mechanisms behind this disease. A fundamental dilemma is the difficulty in identifying clinically important cancers, while they are confined to the prostate gland.Conversely, it is important to identify clinically unimportant cancers so that patients can be spared aggressive treatment. Enhanced understanding of the molecular basis of development of this disease is sorely needed in order to enhance the treatment options and to develop more sensitive and specific prostate cancer diagnostic and prognostic tools.MicroRNA (miRNA) are small non-coding RNA that control gene expression by effectively preventing mRNAs from being translated. The miRNAs play an important role in development and cellular processes such as differentiation, cell growth, cell death and stem cell division, all of which closely linked to cancer.It has been shown that miRNA are aberrantly expressed in several forms of cancer e.g. leukaemia, colon, breast, and lung. Preliminary studies have indicated that the levels of certain miRNAs are altered in prostate cancer. In the proposed study archived tissue samples of prostate tumours and normal tissue will b e used to isolate miRNA that due to their short length are basically unaffected by the harsh fixation and embidding processes these samples have gone through.Differentially displayed miRNAs will be identified using qRT-PCR and confirmed with in situ hybridisation onto tissue microarrays. The biological relevance of the miRNA is confirmed in vitro by introducing anti-miRNA probes, and predicted miRNA targets confirmed.Further, the miRNAs potential in diagnostic use miRNA will be determined on serum samples from prostate cancer patients. This study will combine archive material with clinical data and the latest molecular technologies in order to gain novel information.
Оригинален текст от CORDIS (на английски).
Участници
- LUNDS UNIVERSITET · LUNDКоординаторШвеция
Връзки
Данни: CORDIS, © Европейски съюз