DCUN1D1 promotes tumor progress in prostate cancer and its effect on DU145 in vitro

2020 ◽  
pp. 1-16
Author(s):  
Shun-tan Huang ◽  
Ze-zhen Liu ◽  
Fu-Neng Jiang ◽  
Hui-chan He ◽  
Wei-De Zhong
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Cross Sectional Study ◽  
Molecular Medicine ◽  
Cross Sectional ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Cancer Tissues

Abstract Objective: To compare the expression levels of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene in prostate cancer tissues and normal prostate tissues, to explored its effect on cancerous  cells, and to investigate its underlying mechanisms on such cells in vitro. Methods: The cross-sectional study was conducted at Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics from Jan 03,2017 to Nov 05,2018, and comprised prostate tissue samples on which immunohistochemistry was used to detect the expression of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene. Short hairpin ribonucleic acid expression plasmid targeting the oncogene was constructed and transferred into prostate cance cell line DU145. The roles of the oncogene in prostate cancer progression were confirmed in vitro. The expression of vimentin and epithelial cadherin influenced by the oncogene were detected using Western blot. Data was analysed using SPSS 24. Results: Of the 80 samples, 3(3.75%) were normal prostate tissues, 7(8.75%) adjacent normal prostate tissues, 20(25%) hyperplasia, and 50(62.5%) prostate cancer tissues. Defective In Cullin Neddylation 1 Domain Containing 1 oncogene expression in prostate cancerous tissues was significantly associated with high Gleason score (p<0.001), metastasis (p<0.05) and pathological stage (p<0.001). The oncogene was found to be an independent prognostic factor for disease-free survival of prostate cancer patients (p=0.0108). In vitro analysis confirmed the tumour promotive role of the oncogene through cell proliferation, invasion and migration assays. Continuous...

scholarly journals Long Non-Coding RNA MEG3 Inhibits Cell Proliferation and Induces Apoptosis in Prostate Cancer

2015 ◽  
Vol 37 (6) ◽  
pp. 2209-2220 ◽  
Author(s):  
Gang Luo ◽  
Miao Wang ◽  
Xinchao Wu ◽  
Dan Tao ◽  
Xinyuan Xiao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Regulatory Protein ◽  
Growth Curves ◽  
Underlying Mechanism ◽  
Tumor Tissues ◽  
Cancer Tissues

Background/Aims: Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. Although downregulation of lncRNA maternally expressed gene 3 (MEG3) has been identified in several cancers, little is known about its role in prostate cancer progression. The aim of this study was to detect MEG3 expression in clinical prostate cancer tissues, investigate its biological functions in the development of prostate cancer and the underlying mechanism. Methods: MEG3 expression levels were detected by qRT-PCR in both tumor tissues and adjacent non-tumor tissues from 21 prostate cancer patients. The effects of MEG3 on PC3 and DU145 cells were assessed by MTT assay, colony formation assay, western blot and flow cytometry. Transfected PC3 cells were transplanted into nude mice, and the tumor growth curves were determined. Results: MEG3 decreased significantly in prostate cancer tissues relative to adjacent normal tissues. MEG3 inhibited intrinsic cell survival pathway in vitro and in vivo by reducing the protein expression of Bcl-2, enhancing Bax and activating caspase 3. We further demonstrated that MEG3 inhibited the expression of cell cycle regulatory protein Cyclin D1 and induced cell cycle arrest in G0/G1 phase. Conclusions: Our study presents an important role of MEG3 in the molecular etiology of prostate cancer and implicates the potential application of MEG3 in prostate cancer therapy.

scholarly journals LncRNA AC245100.4 affects the tumorigenesis of prostate cancer via regulating the STAT3/NR4A3 axis

2020 ◽  
Author(s):  
Chi Liu ◽  
Ping Lin ◽  
Jiabin Zhao ◽  
Hui Xie ◽  
Tianhu Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
Rna Immunoprecipitation ◽  
Cancer Tissues ◽  
Promising Avenue

Abstract Background Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of cancer deaths among men globally. However, the molecular mechanisms leading to the progression have not been fully elucidated. Methods The expression and location of AC245100.4 were examined by RT-qPCR and nuclear-cytoplasmic separation assay. RNA-seq analysis was performed to identify the downstream of AC245100.4. RNA immunoprecipitation was performed to identify the proteins those bind to AC245100.4. Western blotting was performed to quantify the expression of proteins. Finally, a series of gain- or loss-functional assays were done to prove the precise role of AC245100.4 and NR4A3 in PCa. Results We identify a critical lncRNA AC245100.4, which is significantly up-regulated in prostate cancer tissues and cells. Knockdown of AC21500.4 can significantly inhibit prostate cancer progression in vitro and in vivo. Further RNA-seq analysis shows that NR4A3 may be the potential target of AC245100.4. Mechanistically, AC245100.4 de-regulates NR4A3 transcriptionally via increasing p-STAT3, which is a transcriptional repressor of NR4A3. Conclusion Our results demonstrated that AC245100.4 was a critically oncogenic lncRNA in PCa via inhibiting NR4A3 and paved a promising avenue to combat PCa progression by targeting AC245100.4 or NR4A3.

scholarly journals Development and Verification of a Prostate Cancer Prognostic Signature Based on an Immunogenomic Landscape Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hong Cheng ◽  
Yi Wang ◽  
Chunhui Liu ◽  
Tiange Wu ◽  
Shuqiu Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Tumor Stages ◽  
Normal Prostate Tissue ◽  
Immune Related Genes

PurposeProstate cancer (PCa) has a high incidence among older men. Until now, there are no immunological markers available to predict PCa patients’ survival. Therefore, it is necessary to explore the immunological characteristics of PCa.MethodsFirst, we retrieved RNA-seq and clinical data of 499 PCa and 52 normal prostate tissue samples from the Cancer Genome Atlas (TCGA). We identified 193 differentially expressed immune-related genes (IRGs) between PCa and normal prostate tissues. Functional enrichment analyses showed that the immune system can participate in PCa initiation. Then, we constructed a correlation network between transcription factors (TFs) and IRGs. We performed univariate and multivariate Cox regression analyses and identified five key prognostic IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1). Finally, a predictive nomogram was established and verified by the C-index.ResultsWe successfully constructed and validated an immune-related PCa prediction model. The signature could independently predict PCa patients’ survival. Results showed that high-immune-risk patients were correlated with advanced stage. We also validated the S100A2 expression in vitro using PCa and normal prostate tissues. We found that higher S100A2 expressions were related to lower biochemical recurrences. Additionally, higher AMH expressions were related to higher Gleason score, lymph node metastasis and positive rate, and tumor stages, and higher ATGR1 expressions were related to lower PSA value.ConclusionOverall, we detected five IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1) that can be used as independent PCa prognostic factors.

Biological role of cytoplasmic transducin beta like related protein 1-induced proliferation and tumorigenicity in prostate cancer

2018 ◽  
Vol 6 (3) ◽  
pp. 223-235
Author(s):  
Shu-Peng Zheng ◽  
Xiang Feng
Keyword(s):  
Prostate Cancer ◽  
Clinical Stage ◽  
Immunohistochemical Analysis ◽  
Related Protein ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Prostate Cell

Androgen receptor mediated transcription and function in prostate cancer and critical for prostate cell growth and gland differentiation. Transducin beta like related protein 1 (TBLR1) primarily localizes in the nucleus in benign prostate tissue and is significantly reduced in prostate cancer. The objective of this study is investigated the role of cytoplasmic TBLR1in prostate cancer. Real-time PCR, Western blotting and immunocytochemistry were used to evaluate Transducin beta like related protein 1 (TBLR1) expression in prostate cancer cell lines and normal prostate cells, tissue samples and adjacent nontumor tissues, and in 142 paraffin-embedded specimens. Immunohistochemical analysis revealed high expression of TBLR1 in 89 of 214 paraffin-embedded archival prostate cancer. The expression level of TBLR1 was significantly increased in prostate cancer both in vivo and in vitro and correlated with clinical stage (P<0.05) and metastasis (P<0.001). Over all the study showed that the TBLR1 plays a key role in the development of prostate cancer cells and TBLR1 may be prognostic marker and a potential therapeutic target in the treatment human prostate cancer.

scholarly journals TFEB Promotes Prostate Cancer Progression via Regulating ABCA2-Dependent Lysosomal Biogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuejin Zhu ◽  
Yangjia Zhuo ◽  
Shulin Wu ◽  
Yanfei Chen ◽  
Jianheng Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Macrophage Polarization ◽  
Clinical Value ◽  
Tissue Samples ◽  
Invasion And Migration

Transcription factor EB (TFEB), a member of the MiT family, is dysregulated in different cancers and exerts specific biological functions within the tumor microenvironment. Downregulation of TFEB induces macrophage polarization in the TME and promotes tumor progression. However, the biological role and clinical significance of TFEB in prostate cancer (PCa) remain unknown. This study aimed to identify the role of TFEB in PCa and its potential clinical value. We explored TFEB expression in PCa using public databases and verified its prognostic value using immunohistochemistry in PCa tissue samples. The results revealed that TFEB expression was up-regulated in PCa tissues and was associated with cancer metastasis. Next, overexpression of TFEB promoted PCa cell malignant behavior in in vivo and in vitro experiments. RNA-sequencing and bioinformatics analysis showed high expression of TFEB promoted lysosomal biogenesis and knockdown of TFEB expression decreased the number of lysosomes. Furthermore, the ATP-binding cassette transporter A2 (ABCA2) was identified as a target gene of TFEB, which was verified using the cleavage under targets and release using nuclease (CUT&amp;RUN) assay and qRT-PCR. Silencing of ABCA2 reduced lysosomal biogenesis and decreased matrix metalloproteinases expression, which reduced PCa cell invasion and migration in the tumor microenvironment. Our study suggests that TFEB promotes PCa progression by regulating ABCA2 through lysosomal biogenesis and may serve as a prognostic factor or as a potential therapeutic target of PCa.

scholarly journals TACR2 is associated with the immune microenvironment and inhibits migration and proliferation via the Wnt/β-catenin signaling pathway in prostate cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wang Jianfeng ◽  
Wang Yutao ◽  
Bi Jianbin
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Clinical Stage ◽  
Wnt Signaling Pathway ◽  
Disease Free Survival ◽  
Normal Prostate ◽  
Tachykinin Receptor ◽  
Protein Levels ◽  
Normal Prostate Tissue ◽  
Cancer Tissues

Abstract Background The tachykinin receptor 2 (TACR2) is encoded by the tachykinin receptor correlation gene. Recent microarray analysis for prostate cancer suggests that TACR2 expression is associated with clinical phenotype and disease-free survival among patients with prostate cancer. Results TACR2 protein levels were lower in prostate cancer tissues than in adjacent normal prostate tissue. TACR2 expression significantly correlated with clinical stage, Gleason scores, and survival outcomes. TACR2 expression positively correlated with mast cells and negatively correlated with M2 macrophages. Overexpression of TACR2 promoted the migration and proliferation of prostate cancer cells by regulating the Wnt signaling pathway. Conclusions The TACR2-Wnt/β-catenin signaling pathway is critical in prostate cancer. TACR2 may affect tumor cells’ occurrence and development by changing the content of immune cells in the tumor microenvironment. These findings suggest that TACR2 may be a candidate molecular biomarker for prostate cancer therapy.

Smoking reduces PSA accuracy for detection of prostate cancer: results from an Italian cross-sectional study

2019 ◽  
Vol 71 (6) ◽  
Author(s):  
Cosimo De Nunzio ◽  
Giorgia Tema ◽  
Alberto Trucchi ◽  
Antonio Cicione ◽  
Angela Sica ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 449
Author(s):  
Simin D. Rezaei ◽  
Joshua A. Hayward ◽  
Sam Norden ◽  
John Pedersen ◽  
John Mills ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Gag Protein ◽  
Protein Levels ◽  
Prostate Epithelial Cells ◽  
Prostate Cancers

Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47–70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker.

scholarly journals EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Common Finding ◽  
Cancer Tissue ◽  
Vulvar Carcinoma ◽  
Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

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