Transcriptional regulation of PRKAR2B by miR-200b-3p/200c-3p and XBP1 in human prostate cancer

In this study, we found that the mutation, copy number alteration, and methylation status of PRKAR2B gene have no correlation with its expression level in PCa. Then, we identified two microRNAs (miR-200b-3p and miR-200c-3p) to be critical regulators of PRKAR2B expression in PCa. Notably, miR-200b-3p and miR-200c-3p expression were significantly downregulated in metastatic CRPC and negatively correlated with the expression level of PRKAR2B in PCa tissues. Moreover, we characterized X-Box Binding Protein 1 (XBP1) as a key transcription factor responsible for PRKAR2B expression in PCa. Importantly, miR-200b-3p/200c-3p or XBP1 knockdown inhibited PCa cell proliferation and promoted cell apoptosis and these inhibitory roles could be largely restored by PRKAR2B, suggesting that PRKAR2B is a functional mediator of miR-200b-3p, miR-200c-3p, and XBP1 in PCa. Collectively, our study firstly identified miR-200b-3p/200c-3p and XBP1 as the critical upstream regulators of PRKAR2B in PCa and provided novel insights to PRKAR2B-driven PCa progression.Graphical abstract
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 21 February 2020Source: Life SciencesAuthor(s): Yunchuanxiang Huang, Guanying Feng, Jingshu Cai, Qian Peng, Zhenglin Yang, Chunhong Yan, Lu Yang, Ziyan WangAbstractAimsProstate cancer (PCa) is the most common type of cancer and a major cause of death in men worldwide. Aberrant Androgen receptor (AR) and PI3K-AKT signaling are very frequent in PCa patients and, therefore, considered as therapeutic targets in the clinic. Sin1 is an essential component of mTORC2 complex, which determines full AKT activation and PCa development in PTEN−/− mice. Here we examined the role of Sin1 in...
Source: Life Sciences - Category: Biology Source Type: research
Abstract Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research
The objective of this study was to identify differentially expressed microRNAs in these cell lines, which may be responsible for the EMT phenotype. Unsupervised hierarchical clustering confirmed that microRNA expression profiles are distinctly different between the two cell lines, with 119 miRNAs significantly increased and 81 microRNAs significantly decreased in ARCaPM cells as compared to ARCaPE. Further analysis revealed that many of the differentially expressed microRNAs belong to only a few microRNA families/clusters. Unsurprisingly, microRNAs in these clusters are co-expressed due to common promoters, which are known...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Homo sapiens Source Type: research
by Shubham Tripathi, Priyanka Chakraborty, Herbert Levine, Mohit Kumar Jolly Epithelial-mesenchymal heterogeneity implies that cells within the same tumor can exhibit different phenotypes—epithelial, mesenchymal, or one or more hybrid epithelial-mesenchymal phenotypes. This behavior has been reported across cancer types, bothin vitro andin vivo, and implicated in multiple processes associated with metastatic aggressiveness including immune evasion, collective dissemination of tumor cells, and emergence of cancer cell subpopulations with stem cell-like properties. However, the ability of a population of cancer cells ...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
Conclusion: We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA. PMID: 32030086 [PubMed]
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research
ConclusionsLncRNA TUG1 plays an oncogenic role in human PCa cells by promoting the cell proliferation and invasion in PCa cell lines, at least partly via the Nrf2 signaling pathway.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
CONCLUSIONS: Our study suggested that TUG1 silencing retarded PCa cell progression in vitro and tumor growth in vivo through miR-128-3p/YES1 axis, showing that targeting TUG1 might be a novel therapeutic strategy for PCa management. PMID: 32016963 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
AbstractThe epithelial –mesenchymal transition (EMT) is a molecular process connected to higher expression of vimentin and increased activity of transcription factors (Snail, Twist) which restrains E-cadherin. EMT has been linked to prostate cancer metastatic potential, therapy resistance, and poor outcomes. Kinetin rib oside (9-(b-dribofuranosyl)-6-furfurylaminopurine, KR) is a naturally occurring cytokinin, which induces apoptosis and shows strong antiproliferative activity against various human cancer cell lines. To establish the effect of KR on human prostate cell lines, expression of, e.g. AR, E-, N-cadherins, V...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
In this study, we hypothesized that heme oxygenase-1 (HO-1), an enzyme responsible for degradation of heme to carbon monoxide (CO), bilirubin, and iron is an important regulator of inflammation and epithelial responses in the prostate. Injection of non-uropathogenic E. coli (MG1655 strain) or PBS into the urethra of mice led to increased numbers of CD45+ leukocytes and mitotic markers (phosphorylated histone H3 and phosphorylated extracellular signal-regulated kinase; Erk1/2) in the prostate glands. Leukocyte infiltration was elevated in prostates harvested from mice lacking HO-1 in the myeloid compartment. Conversely, exo...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
CONCLUSIONS: LncRNA TUG1 plays an oncogenic role in human PCa cells by promoting the cell proliferation and invasion in PCa cell lines, at least partly via the Nrf2 signaling pathway. PMID: 32057513 [PubMed - as supplied by publisher]
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
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