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Titel (primär) MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma
Autor Boll, K.; Reiche, K.; Kasack, K.; Mörbt, N.; Kretzschmar, A.K.; Tomm, J.M.; Verhaegh, G.; Schalken, J.; von Bergen, M.; Horn, F.; Hackermüller, J.;
Journal / Serie Oncogene
Erscheinungsjahr 2013
Department PROTEOM;
Band/Volume 32
Sprache englisch;
POF III (gesamt) F11;
Supplements https://static-content.springer.com/esm/art%3A10.1038%2Fonc.2012.55/MediaObjects/41388_2013_BFonc201255_MOESM24_ESM.pdf
Keywords microRNAs; prostate carcinoma; androgen receptor signaling; MAPK pathway; microRNA targets
UFZ Querschnittsthemen ru3
Abstract

With B30 000 deaths annually in the United States, prostate cancer (PCa) is a major oncologic disease. Here we show that the microRNAs miR-130a, miR-203 and miR-205 jointly interfere with the two major oncogenic pathways in prostate carcinoma and are downregulated in cancer tissue. Using transcriptomics we show that the microRNAs repress several gene products known to be overexpressed in this cancer. Argonaute 2 (AGO2) co-immunoprecipitation, reporter assays and western blot analysis demonstrate that the microRNAs directly target several components of the mitogen-activated protein kinase (MAPK) and androgen receptor (AR) signaling pathways, among those several AR coregulators and HRAS (Harvey rat sarcoma viral oncogene homolog), and repress signaling activity. Both pathways are central for the development of the primary tumor and in particular the progression to its incurable castration-resistant form. Reconstitution of the microRNAs in LNCaP PCa cells induce morphological changes, which resemble the effect of androgen deprivation, and jointly impair tumor cell growth by induction of apoptosis and cell cycle arrest. We therefore propose that these microRNAs jointly act as tumor suppressors in prostate carcinoma and might interfere with progression to castration resistance.
ID 12164
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=12164
Boll, K., Reiche, K., Kasack, K., Mörbt, N., Kretzschmar, A.K., Tomm, J.M., Verhaegh, G., Schalken, J., von Bergen, M., Horn, F., Hackermüller, J. (2013):
MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma
Oncogene 32 , 277 - 285