The combined serum levels of<i>miR-375</i>and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer

Wach, Sven; Al‐Janabi, Omar; Weigelt, Katrin; Fischer, Kersten; Greither, Thomas; Marcou, Marios; Theil, Gerit; Nolte, Elke; Holzhausen, H.-J.; Stöhr, Robert; Huppert, Verena; Hartmann, Arndt; Fornara, Paolo; Wullich, Bernd; Täubert, Helge

doi:10.1002/ijc.29505

Cited by 50 publications

(34 citation statements)

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“…Wachet al reported in 2015 that the expression of miR-375 in 146 PCa patients (median: 1.214) was significantly higher than 35 BPH patients (median: 0.360) and 18 healthy controls (median: 0.405) [20]. Haldrup et al reported that miR-375 level was upregulated by 14.66-fold in serum samples from 31 PCa patients when compared to 13 BPH control patients (p=0.009) [21].…”

Section: Discussionmentioning

confidence: 99%

Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer

Gao¹,

Guo²,

Wang³

et al. 2016

neo

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To investigate the diagnostic potential of plasma miR-21 and miR-375 by comparing their levels in prostate cancer (PCa) patients to subjects without cancer in a Chinese population. The study population included 57 PCa patients and 28 benign prostatic hyperplasia (BPH) patients. The plasma levels of miR-21 and miR-375 were quantitated with Taqman based quantitative real-time polymerase chain reaction. In the BPH group, the median relative expression levels of miR-21 and miR-375 were 0.07 and 0.55, respectively; In the PCa group, the median values of miR-21 and miR-375 were 1.32 and 1.74, respectively. Both miR-21 (p=0.014) and miR-375 (p=0.005) plasma levels were significantly higher in PCa group than in BPH group. Using ROC analysis the AUC of miR-21 was 0.799, 95% CI between 0.690 and 0.908 (p=8×10 -6 ); for miR-375, the AUC was 0.757, 95% CI between 0.640-0.874 (p=0.000126). The largest AUC (0.881) was obtained when the data of miR-21, miR-375 and PSA were combined, with a sensitivity of 87.7% and a specificity of 75%. The results of this study showed that circulating miR-21 and miR-375 can discriminate PCa patients from BPH controls at early stages. Combinations of the studied miRNAs and PSA remarkably increased specificity compared with PSA alone. The combination method has the potential to be used as a noninvasive diagnostic cocktail for PCa screening.

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Section: Discussionmentioning

confidence: 99%

Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer

Gao¹,

Guo²,

Wang³

et al. 2016

neo

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“…miR-375 has been evaluated in this regard. In patients with BPH, no alteration in the plasma level of miR-375 was observed [91].…”

Section: Mir-375mentioning

confidence: 94%

MicroRNAs in Bladder Outlet Obstruction: Relationship to Growth and Matrix Remodelling

Ekman

Albinsson

Uvelius

et al. 2016

Basic Clin Pharma Tox

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The discovery of microRNAs (miRNAs), which are~22 nucleotide RNAs that inhibit protein synthesis in a sequencespecific manner and are present in a range of species, has born hope of new therapeutic strategies. miRNAs play important roles in development and disease, but they remain poorly studied in uropathologies beyond cancer. Here, we discuss biological functions of miRNAs in the lower urogenital tract. A special focus is on miRNAs that change in bladder outlet obstruction (BOO). This is a condition that affects nearly one third of all men over 60 years and that involves growth and fibrosis of the urinary bladder. Animal models of BOO, such as that in rat, have been developed, and they feature a massive 6-fold bladder growth over 6 weeks. Using microarrays, we have charted the miRNAs that change during the time course of this process and identified several with important modulatory roles. We discuss known and predicted functions of miR-1, miR-29, miR-30, miR-132/212, miR-204 and miR-221, all of which change in BOO. The majority of the miRNA-mediated influences in BOO are expected to favour growth. We also outline evidence that miR-29 represents a key effector molecule in a generic response to mechanical distension that is designed to counteract exaggerated organ deformation via effects on matrix deposition and stiffness. We conclude that miRNAs play important roles in bladder remodelling and growth and that they may be targeted pharmacologically to combat diseases of the lower urinary tract.The study of microRNAs (miRNAs) in urodynamic disturbances is a research field in its infancy. A PubMed search for 'microRNA AND bladder NOT cancer' retrieved only 16 titles. This is nothing compared with the thousand or so identified miRNAs in our genomes, or the wealth of data that has accumulated on important homeostatic and pathological functions of this novel class of small RNA molecules. Having identified this paucity of knowledge, we set out to characterize the role of miRNAs in the urinary bladder in a series of recent articles [1][2][3][4]. As a part of this work, we charted changes in bladder miRNA expression after outlet obstruction [2], a condition affecting one third of all men over 60 years. This uncovered a considerable number of deregulated miRNAs with tentative roles in bladder remodelling and growth. These miRNAs are the topic of the current MiniReview. Some aspects of miRNA biology in the urinary bladder have been reviewed elsewhere [5,6]. Biogenesis of MicroRNAsMicroRNAs constitute a class of short, non-coding RNAs that are thought to be involved in the post-translational regulation of most mammalian genes [7]. MicroRNAs are transcribed by RNA polymerase II as long primary (pri)-RNAs that contain cap structures as well as poly(A) tails [8] ( fig.

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“…Characterization of miRNA involvement likely facilitate predictive and prognostic markers of treatments as well as molecular targets for drug development in this stage and tumor type. miR-375 expression in tissue or circulation has been shown to potentially serve as a biomarker for PC diagnosis or prognosis [12–14]. We recently showed significant association of elevated miR-375 levels in plasma with poor overall survival of mCRPC patients [13].…”

Section: Introductionmentioning

confidence: 99%

miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1

et al. 2016

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BackgroundTreatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically are centered on docetaxel-based chemotherapy. We previously reported that elevated miR-375 levels were significantly associated with poor overall survival of mCRPC patients. In this study, we evaluated if miR-375 induced chemo-resistance to docetaxel through regulating target genes associated with drug resistance.MethodsWe first compared miR-375 expression level between prostate cancer tissues and normal prostate tissues using data from The Cancer Genome Atlas (TCGA). To examine the role of miR-375 in docetaxel resistance, we transfected miR-375 using a pre-miRNA lentiviral vector and examined the effects of exogenously overexpressed miR-375 on cell growth in two prostate cancer cell lines, DU145 and PC-3. To determine the effect of overexpressed miR-375 on tumor growth and chemo-resistance in vivo, we injected prostate cancer cells overexpressing miR-375 into nude mice subcutaneously and evaluated tumor growth rate during docetaxel treatment. Lastly, we utilized qRT-PCR and Western blot assay to examine two miR-375 target genes, SEC23A and YAP1, for their expression changes after miR-375 transfection.ResultsBy examining 495 tumor tissues and 52 normal tissues from TCGA data, we found that compared to normal prostate, miR-375 was significantly overexpressed in prostate cancer tissues (8.45-fold increase, p value = 1.98E-23). Docetaxel treatment induced higher expression of miR-375 with 5.83- and 3.02-fold increases in DU145 and PC-3 cells, respectively. Interestingly, miR-375 appeared to play a dual role in prostate cancer proliferation. While miR-375 overexpression caused cell growth inhibition and cell apoptosis, elevated miR-375 also significantly reduced cell sensitivity to docetaxel treatment in vitro, as evidenced by decreased apoptotic cells. In vivo xenograft mouse study showed that tumors with increased miR-375 expression were more tolerant to docetaxel treatment, demonstrated by greater tumor weight and less apoptotic cells in miR-375 transfected group when compared to empty vector control group. In addition, we examined expression levels of the two miR-375 target genes (SEC23A and YAP1) and observed significant reduction in the expression at both protein and mRNA levels in miR-375 transfected prostate cancer cell lines. TCGA dataset analysis further confirmed the negative correlations between miR-375 and the two target genes (r = −0.62 and −0.56 for SEC23A and YAP1, respectively; p < 0.0001).ConclusionsmiR-375 is involved in development of chemo-resistance to docetaxel through regulating SEC23A and YAP1 expression. Our results suggest that miR-375 or its target genes, SEC23A or YAP1, might serve as potential predictive biomarkers to docetaxel-based chemotherapy and/or therapeutic targets to overcome chemo-resistance in mCRPC stage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0556-9) contains supplementary material, which is available to authorize...

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The combined serum levels ofmiR-375and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer

Cited by 50 publications

References 50 publications

Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer

Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer

MicroRNAs in Bladder Outlet Obstruction: Relationship to Growth and Matrix Remodelling

miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1

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