title: TIMP4 expression is regulated by miR-200b-3p in prostate cancer cells.
abstract: In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA-200b-3p. The levels of TIMP4 and miR-200b-3p expression were determined by real time PCR in 27 prostate carcinomas and eight benign prostatic hyperplasia samples. We found that miR-200b-3p positively correlated with TIMP4 expression in cancer samples (r = 0.46; p < 0.02). Moreover, mean miR-200b-3p level and TIMP4 expression were both higher in cancer tissues compared to benign prostatic hyperplasia samples (p > 0.05). Next, to test probable mechanisms of the regulation androgen-sensitive human prostate adenocarcinoma cells (LNCaP) were transfected with synthetic-miR-200b-3p or its synthetic antagonist. Modulation of miR-200b-3p in LNCaP cells had an impact on TIMP4 expression confirming the observation made in analyzed clinical samples. Two targets of miR-200b-3p: ZEB1 and ETS1 were investigated subsequently as potential regulators of TIMP4, however, no effect of their modulation on TIMP4 expression in LNCaP cells was found. Concluding, miR-200b-3p mediates regulation of TIMP4 expression in prostate cancer but exact mechanism needs to be investigated.
authors.affiliation: The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Janiak
authors.affiliation: The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wiktor
authors.initials: W
authors.lastname: Paskal
authors.affiliation: The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.|Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Rak
authors.affiliation: The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Garbicz
authors.affiliation: Clinical Department of Urology and Urological Oncology, Central Clinical Hospital Ministry of Interior in Warsaw, Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Jarema
authors.affiliation: Department of Pathomorphology, Central Clinical Hospital Ministry of Interior in Warsaw, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sikora
authors.affiliation: The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Włodarski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D035683:MicroRNAs; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C533896:MIRN200 microRNA, human
keywords: Prostate cancer; TIMP4; miR-200b-3p