scholarly journals Potential clinical use of miRNA molecules in the diagnosis of prostate cancer

2021 ◽  
Vol 75 ◽  
pp. 491-501
Author(s):  
Paweł Porzycki
Keyword(s):  
Prostate Cancer ◽  
Gene Expression Regulation ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Process ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Diagnostic Tools ◽  
Transcriptional Level ◽  
Mesenchymal Transition

Prostate cancer (PCa) is the most common type of cancer among men in Europe and this applies to almost the whole world. Current recommendations for screening and diagnosis are based on prostate specific antigen (PSA) measurements and the digital rectal examination (DRE). Both of them trigger the prostate biopsy. Limited specificity of the PSA test brings, however, a need to develop new and better diagnostic tools. In the last few years, new approaches for providing significantly better biomarkers, an alternative to PSA, have been introduced. Modern biomarkers show improvement not only as a diagnostic procedure, but also for staging, evaluating aggressiveness and managing the therapeutic process. The most promising group are molecular markers; among them microRNAs (miRNAs, miRs) are most frequent. miRNAs represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. This article reports a revision about the role of miRNAs in PCa including data of Adreno Receptor (AR) signaling, cell cycle, epithelial mesenchymal transition (EMT) process, cancer stem cells (CSCs) regulation and even the role of miRNAs as PCa therapeutic tool. Finding better PCa biomarkers, replacing the current PSA measurement, is firmly needed in modern oncology practice.

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

scholarly journals Correction to: Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Inhibitory Role

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 434 ◽  
Author(s):  
Wenjuan Mei ◽  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Yan Gu ◽  
Kuncheng Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Current Evidence ◽  
Target Cells ◽  
Mesenchymal Transition ◽  
Prostate Cancer Stem Cells

Research in the last decade has clearly revealed a critical role of prostate cancer stem cells (PCSCs) in prostate cancer (PC). Prostate stem cells (PSCs) reside in both basal and luminal layers, and are the target cells of oncogenic transformation, suggesting a role of PCSCs in PC initiation. Mutations in PTEN, TP53, and RB1 commonly occur in PC, particularly in metastasis and castration-resistant PC. The loss of PTEN together with Ras activation induces partial epithelial–mesenchymal transition (EMT), which is a major mechanism that confers plasticity to cancer stem cells (CSCs) and PCSCs, which contributes to metastasis. While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs. TP53 and RB1 suppress lineage plasticity through the inhibition of SOX2 expression. In this review, we will discuss the current evidence supporting a major role of PCSCs in PC initiation and metastasis, as well as the underlying mechanisms regulating PCSCs. These discussions will be developed along with the cancer stem cell (CSC) knowledge in other cancer types.

scholarly journals Role of a novel race-related tumor suppressor microRNA located in frequently deleted chromosomal locus 8p21 in prostate cancer progression

2019 ◽  
Vol 40 (5) ◽  
pp. 633-642 ◽  
Author(s):  
Divya Bhagirath ◽  
Thao Ly Yang ◽  
Z Laura Tabatabai ◽  
Varahram Shahryari ◽  
Shahana Majid ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Tumor Grade ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Microrna Genes

Abstract The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21–22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes—miR-3622, miR-3622b, miR-383—that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p—miR-4288—by employing clinical samples and cell lines. Our data suggests that (i) miR-4288 is widely downregulated in primary prostate tumors and cell lines; (ii) miR-4288 expression is lost in metastatic castration-resistant PCa; (ii) miR-4288 downregulation is race-related PCa alteration that is prevalent in Caucasian patients and not in African Americans; (iii) in Caucasians, miR-4288 was found to be associated with increasing tumor grade and high serum prostate-specific antigen, suggesting that miR-4288 downregulation/loss may be associated with tumor progression specifically in Caucasians; (iv) miR-4288 possess significant potential as a molecular biomarker to predict aggressiveness/metastasis; and (v) miR-4288 is anti-proliferative, is anti-invasive and inhibits epithelial-to-mesenchymal transition; and (vi) miR-4288 directly represses expression of metastasis/invasion-associated genes MMP16 and ROCK1. Thus, the present study demonstrates a tumor suppressor role for a novel miRNA located with a frequently lost region in PCa, strengthening our hypothesis that this locus is causally related to PCa disease progression via loss of microRNA genes. Our study suggests that miR-4288 may be a novel biomarker and therapeutic target, particularly in Caucasians.

scholarly journals Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Common Disease ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
Endothelial Growth Factor ◽  
E Cadherin

Abstract Background Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa. Methods Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected. Results miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis. Conclusions The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial–mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

The Association of PSA-IGM and Total PSA Improves the Diagnosis of Prostate Cancer

2009 ◽  
Vol 24 (3) ◽  
pp. 212-212
Author(s):  
Danilo Zani ◽  
Silvia Costa ◽  
Lorenzo Gatti ◽  
Nicola Pesenti ◽  
Alberto Pettenò ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Accuracy ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Serum Levels ◽  
Immunoglobulin M ◽  
Diagnostic Tools ◽  
Psa Test ◽  
Total Psa

Background and aim The specific causes of prostate cancer (Pca) are unknown but the main risk factors of tumor development are associated with age, genetic factors, ethnicity, diet and lifestyle. Prostate cancer is rare in men under 45 years of age, but becomes more common with advancing age. The main diagnostic tools for demonstrating the presence of PCa include digital rectal examination, transrectal ultrasonography, and serum measurement of prostate specific antigen (PSA) followed by prostate biopsy for confirmation of the diagnosis. While the measurement of PSA levels has revolutionized the diagnosis of PCa, it has also increased its overdiagnosis due to the poor diagnostic accuracy. Scientific evidence indicates that biomarkers for different types of cancer such as liver and colorectal cancer circulate in the blood associated with immunoglobulin M (IgM) to form complexes that allow a better diagnosis in comparison to circulating free biomarkers. In prostate cancer it has been demonstrated that testing for serum levels of the PSA-IgM immune complex improves the diagnostic performance of total PSA. The aim of this study was to evaluate the diagnostic accuracy of PSA-IgM compared to total PSA for the selection of patients to be submitted to transrectal ultrasound-guided prostate biopsy. Patients and methods Serum samples from 67 male patients, 33 affected by PCa with a Gleason score from 5 to 7, and 34 affected by benign prostate hypertrophy (BPH), were collected by the Department of Urology of the Spedali Civili of Brescia. The samples were immediately snap frozen at −80°C. Serum levels of PSA-IgM were assessed using Prostate-IC (Xeptagen, Italy) while PSA levels were determined with the Immulite 2000 of Medical Systems S.p.A. Results Patients were stratified into 2 groups according to age; the first group consisted of 24 patients with PCa and 20 with BPH aged between 60 and 70 years and the second group consisted of 9 patients with PCa and 14 with BPH aged between 70 and 80 years. Serum levels of PSA and PSA-IgM were analyzed in the 2 groups using cutoff values of 4 ng/mL for PSA and 145 AU/mL for PSA-IgM. In the first group, 1 8 of 24 PCa patients were positive for PSA (75% sensitivity) with a specificity of 50% (10 of 20 BPH patients), and 1 0 of 24 PCa patients were positive with the PSA-IgM assay (42% sensitivity), which had a higher specificity (70%; 6 of 20 BPH patients). The combination of both biomarkers resulted in a sensitivity of 38% (9 of 24 patients with PCa) but showed a significant improvement in specificity up to 90%, since 18 of 20 patients with BPH were negative for at least one test. In the second group of patients aged 70 to 80 years, the PSA test had a sensitivity of 67% (6/9 PCa patients) and a specificity of 78% (3/14 BPH patients) compared with a sensitivity of 44% for the PSA-IgM test (4/9 PCa patients) with a specificity of 71% (4/14 BPH patients). The combination of PSA and PSA-IgM had a sensitivity of 30% (3/9) but the highest specificity (93%, 13/14 BPH patients). Conclusion The results of the study demonstrate the diagnostic value of the PSA-IgM assay compared with the total PSA test. The combination of PSA-IgM with total PSA was the best approach to reduce the number of false-positive results, thus improving the diagnosis of prostate cancer.

scholarly journals MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression

2022 ◽  
Vol 36 ◽  
pp. 205873842110586
Author(s):  
Yan Zhang ◽  
Min Zhou ◽  
Kun Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Transcriptional Level ◽  
Human Ovarian Cancer ◽  
Mesenchymal Transition

Introduction MicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer. Methods Cell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression. Results The results revealed significant ( p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly ( p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly ( p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial–mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells. Conclusion Taken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer

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