Metastatic prostate cancer is a lethal disease that remains incurable despite the recent approval of new drugs, thus making the development of alternative treatment approaches urgently needed. A more precise understanding of the molecular mechanisms underlying prostate cancer dissemination could lead to the identification of novel therapeutic targets for the design of efficient anti-metastatic strategies. MicroRNA (miRNAs) are endogenous, small non-coding RNA molecules acting as key regulators of gene expression at post-transcriptional level. It has been clearly established that altered miRNA expression is a common hallmark of cancer. In addition, emerging evidence suggests their direct involvement in the metastatic cascade. In this review, we present a comprehensive overview of the data generated in experimental tumor models indicating that specific miRNAs may impinge on the different stages of prostate cancer metastasis, including (i) the regulation of epithelial-to-mesenchymal transition and cell migration/invasion, (ii) the interplay between cancer cells and the surrounding stroma, (iii) the control of angiogenesis, (iv) the regulation of anoikis, and (v) the colonization of distant organs. Moreover, we show preliminary evidence of the clinical relevance of some of these miRNAs, in terms of association with tumor aggressiveness/dissemination and clinical outcome, as emerged from translation studies carried out in prostate cancer patient cohorts. We also discuss the potential and the current limitations of manipulating metastasis-related miRNAs, by mimicking or inhibiting them, as a strategy for the development of novel therapeutic approaches for the advanced disease.
Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and...
#1Jiajia Yang(MOE: Chinese Ministry of Education)H-Index: 3
#2Yixuan Hou(MOE: Chinese Ministry of Education)H-Index: 15
Last. Manran Liu(MOE: Chinese Ministry of Education)H-Index: 22
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Abstract Twist, a highly conserved basic Helix-Loop-Helix transcription factor, functions as a major regulator of epithelial-mesenchymal transition (EMT) and tumor metastasis. In different cell models, signaling pathways such as TGF-β, MAPK/ERK, WNT, AKT, JAK/STAT, Notch, and P53 have also been shown to play key roles in the EMT process, yet little is known about the signaling pathways regulated by Twist in tumor cells. Using iTRAQ-labeling combined with 2D LC–MS/MS analysis, we identified 194 p...
Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, mig...
Aberrant expression of miRNAs is critically implicated in cancer initiation and progression. Therapeutic approaches focused on regulating miRNAs are therefore a promising approach for treating cancer. Antisense oligonucleotides, miRNA sponges, and CRISPR/Cas9 genome editing systems are being investigated as tools for regulating miRNAs. Despite the accruing insights in the use of these tools, delivery concerns have mitigated clinical application of such systems. In contrast, little attention has ...
// Lin Wang 1 , Guanhua Song 2 , Weiwei Tan 3 , Mei Qi 3 , Lili Zhang 3 , Jonathan Chan 4 , Jindan Yu 5 , Jinxiang Han 1 , Bo Han 3, 6 1 Research Center for Medicinal Biotechnology, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, China 2 Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China 3 Department of Pathology, Shandong University Medical School, Jinan, China 4 Department of Immunology, University of...
Last. Jianxiu Yu(SJTU: Shanghai Jiao Tong University)H-Index: 25
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Prostate cancer (PCa) is the most prevalent malignant carcinoma among males in western countries. Currently no treatments can cure advanced prostate cancers, so new diagnostic and therapeutic strategies are in urgent need. At present limited knowledge is available concerning the roles of dysregulated microRNAs in prostate cancer metastasis. In this study, we found that the expression of miR-130b was significantly down-regulated in prostate cancer cell lines and clinical prostate cancer tissues. ...
Since 2010, multiple advances have been made in the field of metastatic castration-resistant prostate cancer including regulatory approvals for five new agents including androgen pathway inhibitors (enzalutamide, abiraterone acetate), immunotherapy (sipuleucel-T), cytotoxic chemotherapy (cabazitaxel) and radiopharmaceuticals (radium-223) that have improved overall survival in this patient population. Despite these advances, each therapy has only extended median survival by 3–5 months and data su...
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 i...
BACKGROUND Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development. METHODS Initially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a ...
Cancer development and progression are not solely cell-autonomous and genetically driven processes. Dynamic interaction of cancer cells with the surrounding microenvironment, intended as the chemical/physical conditions as well as the mixture of non-neoplastic cells of the tumor niche, drive epigenetic changes that are pivotal for the acquisition of malignant traits. Cancer-associated fibroblasts (CAF), namely fibroblasts that, corrupted by cancer cells, acquire a myofibroblast-like reactive phe...
Prostate cancer (PCa) is one of the most common malignancies for men worldwide, and abnormal activation of the androgen receptor (AR) signaling plays an important role in the progression of PCa. However, in the androgen deprivation therapy (ADT), AR signaling inevitably recovered, as a result, exploring novel regulating mechanisms is of great importance. Recently, non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, circular RNAs, could be involved in the progression of PCa, and ...
#1Fubo Wang('SMMU': Second Military Medical University)H-Index: 15
#2Wei Zhang('SMMU': Second Military Medical University)H-Index: 12
Last. Rui Chen('SMMU': Second Military Medical University)H-Index: 17
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BACKGROUND To identify novel miRNAs implicated in prostate cancer metastasis. METHODS Sixty-five prostate cancer tissues and paired pan-cancer tissues were sequenced. Novel miRNAs were re-analyzed by MIREAP program. Biological functions of miR-N5 were transwell experiment and colony formation. Target genes of miR-N5 were analyzed by bioinformatic analysis. Downstream of target gene was analyzed by The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases and con...
#1Tyler Sheetz(OSU: Ohio State University)H-Index: 5
#1Tyler Sheetz(The Ohio State University Wexner Medical Center)
Last. Dario Palmieri(OSU: Ohio State University)H-Index: 24
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Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a singl...
#2Mingquan Gao(University of Electronic Science and Technology of China)H-Index: 1
Last. Fuchun Jiang('SMMU': Second Military Medical University)H-Index: 1
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Abstract Objectives Prostate cancer, one of the most frequently diagnosed tumors of men, leads to poor quality of life. Previous studies have shown that breviscapine (BRE) exerts therapeutic activity in malignant tumors. However, the role and mechanism of BRE exhibit an anti-tumor effect on prostate cancer are largely unknown. Methods The mRNA and protein levels in prostate cancer tissues and cell lines were measured using RT-qPCR, western blot, and immunohistochemical staining, respectively. Ce...
#2Yue Kuai(SRRSH: Sir Run Run Shaw Hospital)H-Index: 2
Last. Qixin Chen(ZJU: Zhejiang University)H-Index: 17
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Prostate cancer (PCa) is the leading cause of cancer-related death among men worldwide. Knowledge of the prognostic factors of PCa and the bone metastasis pattern of patients would be helpful for patients and doctors. The data of 177,255 patients with prostate cancer diagnosed between 2010 and 2013 with at least five years of follow-up were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determine the predictive val...
: Prostate cancer (PCa) is one of the most common types of cancer in men. In several recent studies, chromosomal deletions in the q arm of chromosome 2, where ING5 resides within, have been identified in various cancer types including PCa. In this study, we investigate the role of ING5 as a tumor suppressor in PCa. We examined the expression level of ING5 in tissue samples and cell lines using quantitative real-time polymerase chain reaction and western blot analysis. We tested the in vitro tumo...
Last. Zhixin Wang(JLU: Jilin University)H-Index: 6
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Background: Prostate cancer is one of the most commonly diagnosed diseases in males. Methods: RT-qPCR was used to detect miR-129-5p expression in tumor tissues and adjacent normal tissues from patients with prostate cancer. The cell proliferation assay and colony forming assay were used to study the role of miR-129-5p in mediating prostate cancer cell growth. Bioinformatic analysis and dual luciferase assay were performed to predict and confirm ETV1 as a target gene of miR-129-5p. Results: We fo...