AbstractmiRNAs have proven to be key regulators of gene expression and are differentially expressed in various diseases, including cancer. Our aim was to identify epigenetically dysregulated genes in prostate cancer. We performed miRNA expression profiling after relieving epigenetic modifications in 6 prostate cancer cell lines and nonmalignant prostate epithelial cells. Thirty‐eight miRNAs showed increased expression in any prostate cancer cell line after 5‐aza‐2′‐deoxycytidine (5azadC) and trichostatin A (TSA) treatments. Six of these also had decreased expression in clinical prostate cancer samples compared to benign prostatic hyperplasia. Among these, miR‐193b was methylated in 22Rv1 cell line at a CpG island ∼1 kb upstream of the miRNA locus. Expressing miR‐193b in 22Rv1 cells using pre‐miR‐193b oligonucleotides caused a significant growth reduction (p < 0.001) resulting from a decrease of cells in S‐phase of the cell cycle (p < 0.01). In addition, the anchorage independent growth was partially inhibited in transiently miR‐193b‐expressing 22Rv1 cells (p < 0.01). Altogether, our data suggest that miR‐193b is an epigenetically silenced putative tumor suppressor in prostate cancer.
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BackgroundThe fungal genus Phlebia consists of a number of species that are significant in wood decay. Biotechnological potential of a few species for enzyme production and degradation of lignin and pollutants has been previously studied, when most of the species of this genus are unknown. Therefore, we carried out a wider study on biochemistry and systematics of Phlebia species.MethodsIsolates belonging to the genus Phlebia were subjected to four-gene sequence analysis in order to clarify their phylogenetic placement at species level and evolutionary relationships of the genus among phlebioid Polyporales. rRNA-encoding (5.8S, partial LSU) and two protein-encoding gene (gapdh, rpb2) sequences were adopted for the evolutionary analysis, and ITS sequences (ITS1 + 5.8S + ITS2) were aligned for in-depth species-level phylogeny. The 49 fungal isolates were cultivated on semi-solid milled spruce wood medium for 21 days in order to follow their production of extracellular lignocellulose-converting oxidoreductases and carbohydrate active enzymes.ResultsFour-gene phylogenetic analysis confirmed the polyphyletic nature of the genus Phlebia. Ten species-level subgroups were formed, and their lignocellulose-converting enzyme activity profiles coincided with the phylogenetic grouping. The highest enzyme activities for lignin modification (manganese peroxidase activity) were obtained for Phlebia radiata group, which supports our previous studies on the enzymology and gene expression of this species on lignocellulosic substrates.ConclusionsOur study implies that there is a species-level connection of molecular systematics (genotype) to the efficiency in production of both lignocellulose-converting carbohydrate active enzymes and oxidoreductases (enzyme phenotype) on spruce wood. Thus, we may propose a similar phylogrouping approach for prediction of lignocellulose-converting enzyme phenotypes in new fungal species or genetically and biochemically less-studied isolates of the wood-decay Polyporales.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0538-x) contains supplementary material, which is available to authorized users.
Amplification of the long arm of chromosome 8 is one of the most recurrent findings in prostate cancer and it is associated with poor prognosis. Several minimal regions of amplification suggest multiple target genes which are yet to be identified. We have previously shown that TCEB1, EIF3S3, KIAA0196 and RAD21 are amplified and overexpressed in prostate cancer and they are located in the 8q area. In this study, we examined the functional effects of these genes to prostate cancer cell phenotype. We overexpressed and inhibited the genes by lentivirus mediated overexpression and RNA interference, respectively. shRNA mediated TCEB1 silencing decreased significantly cellular invasion of PC-3 and DU145 cells through Matrigel. TCEB1 silencing reduced the anchorage-independent growth of PC-3 cells. Similar effects were not seen with any other genes. When overexpressed in NIH 3T3 cells, TCEB1 and EIF3S3 increased the growth rate of the cells. Transcriptional profiling of TCEB1 silenced PC-3 cells revealed decrease of genes involved in invasion and metastasis. Finally, we also confirmed here the overexpression of TCEB1 in hormone-refractory prostate tumors. This study indicates that TCEB1 promotes invasion of prostate cancer cells, is involved in development of hormonerefractory prostate cancer and is thereby a strong candidate to be one of the target genes for the 8q gain. ' 2008 Wiley-Liss, Inc.Key words: prostatic carcinoma; RNAi; elongin C Prostate cancer is the most common male malignancy in Western countries and the second most common cause of cancer related deaths in males.1 Because of the intensive research in the past years main chromosomal aberrations in prostate cancer have been revealed, but hunting for many of the target genes is still in process. Gain of the long arm of chromosome 8 (8q) is one of the most recurrent findings in advanced prostate tumors and it is associated with poor prognosis. 2,3Several minimal regions of amplification of 8q have been identified by comparative genomic hybridization (CGH) and array-CGH, suggesting several target genes. Two of these minimal regions are 8q21 and 8q23-24. [4][5][6] We have identified 4 genes that are amplified and highly expressed in prostate cancer and located in these regions. One of them, TCEB1 [transcription elongation factor B (SIII), polypeptide 1 (15 kDa, elongin C)] is located in 8q21.11 and others RAD21 [RAD21 homolog (S. pombe)], KIAA0196 and EIF3S3 (eukaryotic translation initiation factor 3, subunit H) in 8q23-24. 7-9TCEB1 was found to be amplified in 20% of hormone-refractory prostate tumors. Although in untreated primary tumors no gene amplification was found, low-level gains were found in about 30% of the tumors. In PC-3 cell line, which contains the TCEB1 gene amplification, the expression is 5 times higher compared to cell lines with no amplification.7 RAD21 is amplified in 30% of hormone-refractory carcinomas and it is expressed significantly more in untreated prostate carcinomas than in benign prostate hyperplasia (BPH). Also KIAA0196 is amp...
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