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 Long non-coding RNA TUSC7 suppressed colorectal cancer progression via regulation of miR-23b/PDE7A Axis

2020 ◽  
Vol 43 (4) ◽  
pp. E35-43
Author(s):  
Lingfang Hao ◽  
Yaofeng Yun ◽  
Run Liang ◽  
Gang Yuan
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Progression

Purpose: Despite advances in our understanding of the roles of the long noncoding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified to act as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle and tumor growth, its function in colorectal cancer remains unknown. Methods: The expression levels of TUSC7 in colorectal cancer tissues and cell lines were determined, and the biological functions of TUSC7 to cancer progression in colorectal cancer were investigated via correlation analysis of clinical samples, cell viability assay, transwell assay and apoptosis analysis. Further, the molecular regulatory mechanisms of TUSC7 were demonstrated by luciferase reporter assay and western blotting. Results: We observed that the expression of TUSC7 was markedly decreased in colorectal cancer cell lines. Moreover, the lower expression of TUSC7 was correlated with advanced clinical grades and poorer survival and may be an independent risk factor for colorectal cancer. Moreover, the expression of TUSC7 inhibited cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT), while it facilitated apoptosis through competitively binding miR-23b. We also found that TUSC7 decreased the expression of phosphodiesterase 7A (PDE7A), a downstream target of miR-23b, through the TUSC7/miR-23b/PDE7A axis. Conclusion: We demonstrated the expression of TUSC7 suppressed colorectal cancer progression through the TUSC7/miR-23b/PDE7A axis, suggesting that TUSC is a potential target for therapeutic intervention in colorectal cancer.

An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Miltiadis Paliouras ◽  
Eleftherios P. Diamandis
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Intracellular Signaling ◽  
Specific Antigen ◽  
Independent State ◽  
Epidermal Growth ◽  
Androgen Independent

AbstractThe androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancerin vitromodel. Using the cell line PC3(AR)2, we stimulated cells with 5-α-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)2cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose anin vitroandrogen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

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.

The relationship of HIF2 and the progression of PTEN-deficient mouse prostate tumors.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 30-30
Author(s):  
W. Y. Kim ◽  
B. Zhou ◽  
G. Thomas
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Deficient Mouse ◽  
Prostate Cancer Progression ◽  
Prostate Tumors ◽  
Mesenchymal Transition

30 Background: The hypoxia-inducible factor (HIF) transcription factor has already cemented its oncogenic role in the development of renal cell carcinoma (RCC). However, its role in the tumorigenesis of other solid tumors remains unspecificed. Our studies focus on a novel link between HIF and prostate carcinogenesis. Methods: Using both in vitro cell culture studies as well as in vivo studies (orthotopic xenograft and genetically engineered mouse models) we investigate the role of HIF in prostate cancer cell proliferation, invasion, and progression. Results: Both HIF1 and HIF2 appear to be necessary for the proliferation and invasion of prostate cancer cell lines in vitro. Preliminary analysis of a PTEN deficient mouse model of prostate cancer suggests that expression of a stabilized form of HIF2 promotes the development of a larger prostate tumor burden and a more aggressive histology (high grade prostate intraepithelial neoplasia [PIN] at earlier stages). Moreover, PTEN-deficient prostate tumors producing HIF2 are more proliferative and vascular and express increased levels of genes associated with epithelial to mesenchymal transition (EMT). Conclusions: There has been much interest in the role of angiogenesis and hypoxia in prostate cancer progression. Our preliminary data suggest that HIF2 is able to promote PTEN-deficient prostate cancer progression in mice by increasing proliferation, angiogenesis, and EMT. No significant financial relationships to disclose.

scholarly journals CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhenkun Ma ◽  
Ye Gao ◽  
Wei Liu ◽  
Long Zheng ◽  
Ben Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Progression ◽  
Metalloprotease Activity ◽  
A Disintegrin And Metalloproteinase ◽  
Cancer Tissues ◽  
Inhibitory Regulation ◽  
E Cadherin

CD82 acts as a tumor suppressor in a series of steps in malignant progression. Here, we identified a novel function of CD82 on posttranslational regulating E-cadherin in prostate cancer. In our study, the declined expression of CD82 was verified in prostate cancer tissues and cell lines compared with normal tissue and cell lines. Functionally, CD82 inhibited cell migration and E-cadherin cleavage from the cell membrane in prostate cancer cell. Further study proved that a disintegrin and metalloproteinase ADAM17 as an executor of E-cadherin cleavage mediated the inhibitory regulation of CD82 in E-cadherin shedding in prostate cancer. Specifically, CD82 interacted with ADAM17 and inhibited its metalloprotease activity, which led to the descent of E-cadherin shedding. These results show a nuanced but important role of CD82 in nontranscriptional regulation of E-cadherin, which may help to understand the intricate regulation of dysfunctional adhesion molecule in cancer progression.

scholarly journals The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 235 ◽  
Author(s):  
Simona Pellecchia ◽  
Romina Sepe ◽  
Myriam Decaussin-Petrucci ◽  
Cristina Ivan ◽  
Masayoshi Shimizu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
P Value ◽  
Thyroid Carcinomas ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
E Cadherin

Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis.

scholarly journals UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition

2019 ◽  
Vol 8 (4) ◽  
pp. 560 ◽  
Author(s):  
Javier Martinez-Useros ◽  
Nuria Garcia-Carbonero ◽  
Weiyao Li ◽  
Maria J. Fernandez-Aceñero ◽  
Ion Cristobal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Progression

CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.

scholarly journals LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

2021 ◽  
Author(s):  
Chuigong Yu ◽  
Yu Fan ◽  
Yu Zhang ◽  
Lupeng Liu ◽  
Gang Guo
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Janus Kinase ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Abstract Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa.Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules.Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

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