BPA-induced prostatic hyperplasia in vitro is correlated to the unbalanced gene expression of AR and ER in the epithelium and stroma

As a typical environmental endocrine disruptor (EED), bisphenol A (BPA) can induce pathological hyperplasia of the prostatic epithelium and stroma. This study concentrates mainly on the effect and underlying mechanisms of BPA on prostatic hyperplasia, which is based on the culture of primary human prostate epithelial cells (HPEpiC) and human prostate fibroblasts (HPrF). In an effect to screen the optimal pro-survival BPA levels, HPEpiC and HPrF were, respectively, exposed to concentration gradients of BPA (10−12 M–10−4 M) solution diluted with two corresponding medium and incubated for 72 h at 37°C. CCK-8 assay showed that 10−9 M–10−5 M BPA could facilitate the proliferation of HPEpiC, while similar proliferative effect of HPrF only needed 10−11 M–10−7 M BPA. HPrF were more sensitive to BPA than HPEpiC. The qualification of PCNA gene expression measured using quantitative real-time polymerase chain reaction (qRT-PCR) also mirrored the BPA-induced cell proliferation. Additionally, our results considered that androgen receptor (AR), estrogen receptor (ERα, ERβ), and NFKB1 gene expressions exhibited up-regulation in HPEpiC treated with 10−9 M BPA for 72 h. However, in HPrF, the identical BPA treatment could activate ERα, ERβ, and NFKB1 gene expressions and down-regulated the expression of AR levels. It is further confirmed that low-dose BPA can indeed promote the proliferation of human prostate cells in vitro, and the mechanisms of BPA for prostatic epithelial and stromal hyperplasia may not be consistent.

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CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway

Cancer Cell International ◽

10.1186/s12935-021-02120-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Xie ◽

Xiaofeng Hang ◽

Wensheng Xu ◽

Jing Gu ◽

Yuanjing Zhang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

In Vivo Studies ◽

Circular Rnas ◽

Novel Target ◽

Underlying Mechanisms

Abstract Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

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Abstract 41: Explant-Derived Cells from Chronic Heart Failure Activated Endothelial-Mesenchymal Transition and Attenuated Pluripotency Genes Expression

Circulation Research ◽

10.1161/res.111.suppl_1.a41 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Liudmila Zakharova ◽

Hikmet Nural ◽

Mohamed A Gaballa

Keyword(s):

Gene Expression ◽

Progenitor Cells ◽

Smooth Muscle Actin ◽

Fold Increase ◽

Gene Expressions ◽

Mesenchymal Transition ◽

Cell Outgrowth ◽

Pluripotency Genes

Cardiac progenitor cells are generated from atria explants; however the cellular origin and the mechanisms of cell outgrowth are unclear. Using transgenic tamoxifen-induced Willms tumor 1 (Wt1)-Cre/ERT and Cre-activated GFP reporter mice, we found approximately 40% of explant-derived cells and 74% of explant-derived c-Kit+ cells originated from the epicardium. In atria from sham hearts, Wt1+ cells were located in a thin epicardial layer, while c-Kit+ cells were primarily found within both the sub-epicardium and the myocardium, albeit at low frequency. No overlap between c-Kit+ and Wt1+ cells was observed, suggesting that epicardial Wt1+ cells do not express c-Kit marker in vivo, but more likely the c-Kit marker was acquired in culture. Compared with 4 days in culture, at day 21 we observed 7 folds increase in Snail gene expression; 32% increase in α-smooth muscle actin (SMA) marker, and 30% decrease in E-cadherin marker, suggesting that the explant-derived cells underwent epithelial to mesenchymal transition (EMT) in vitro. Cell outgrowths released TGF-β (1036.4 ± 1.18 pm/ml) and exhibited active TGF-β signaling, which might triggered the EMT. Compared to shams, CHF cell outgrowths exhibited elevated levels of EMT markers, SMA (49% vs. 34%) and Snail (2 folds), and reduced level of Wt1 (11% vs. 22%). In addition, CHF cell outgrowths had two folds increase in Pai1 gene expression, a direct target of TGF-β signaling. In c-Kit+ cells derived from CHF explants, Nanog gene expression was 4 folds lower and Sox 2 was 2 folds lower compared with cells from shams. Suppression of EMT in cell outgrowth increased the percentage of c-Kit+ and Wt1+ cells by 17%, and 15%, respectively. Also suppression of EMT in c-Kit+ cells resulted in 4 folds increase in Nanog and 3 fold increase in Sox2 gene expressions. Our results showed that CHF may further exuberates EMT while diminishes the re-activation of pluripotency genes. Thus, EMT modulation in CHF is a possible strategy to regulate both the yield and the pluripotency of cardiac-explant-derived progenitor cells.

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HDAC6 inhibitor WT161 performs antitumor effect on osteosarcoma and synergistically interacts with 5-FU

Bioscience Reports ◽

10.1042/bsr20203905 ◽

2021 ◽

Author(s):

Jun Sun ◽

Wei Wu ◽

Xiaofeng Tang ◽

Feifei Zhang ◽

Cheng Ju ◽

...

Keyword(s):

Dependent Manner ◽

Osteosarcoma Cells ◽

Synergistic Inhibition ◽

Proliferative Effect ◽

Xenograft Models ◽

Hdac6 Inhibitor ◽

Underlying Mechanisms ◽

Induced Apoptosis

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of this study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of AKT. More importantly, WT161 show synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

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Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0240339 ◽

2000 ◽

Vol 24 (3) ◽

pp. 339-351 ◽

Cited By ~ 36

Author(s):

AS Waller ◽

RM Sharrard ◽

P Berthon ◽

NJ Maitland

Keyword(s):

Androgen Receptor ◽

In Vitro Models ◽

Human Prostate ◽

Intracellular Targeting ◽

Natural Ligand ◽

Prostate Cells ◽

Established Cell ◽

Prostatic Epithelium ◽

Prostate Epithelium

In vitro models of normal and malignant human prostate are currently limited to a few well established cell lines that, with a single exception (LNCaP), fail to express the androgen receptor (AR) - a common characteristic of prostatic epithelium grown in culture. To investigate the molecular mechanism of action of the non-steroidal antiandrogen Casodex (bicalutamide) against wild-type AR, we have established a transient AR expression model in non-tumorigenic prostate cells of both epithelial and mesenchymal origin. In this model, both dihydrotestosterone and Casodex can effectively transport the AR protein into the nucleus of prostate cells. Whereas the natural ligand, dihydrotestosterone, stabilises the receptor, the AR is rapidly degraded at a nuclear location when the transfected cells are treated with Casodex. In contrast, whereas the mutant AR in the LNCaP line is also degraded on Casodex treatment over the same time period, its intracellular targeting is defective.

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Bidirectional Oscillatory Shear Stress Increases Pro-Atherogenic Gene Expressions (I-CAM1, E-Selectin and IL-6) in Endothelial Cells

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53747 ◽

2011 ◽

Author(s):

Amlan Chakraborty ◽

Venkatakrishna R. Jala ◽

Sutirtha Chakraborty ◽

R. Eric Berson ◽

M. Keith Sharp ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Shear Stress ◽

Atherosclerotic Plaque ◽

Inflammatory Diseases ◽

Leukotriene B4 ◽

Oscillatory Shear ◽

Gene Expressions

Wall shear stress (WSS) plays a key role in altering intracellular pathways and gene expression of endothelial cells, and has significant impacts on atherosclerotic plaque development (1–3). Further, the atherogenic regulators Leukotriene B4 (LTB4) and Lipopolysaccharide (LPS) have significant impacts on the pathophysiology of many inflammatory diseases. This study investigates the effects of oscillatory shear directionality on pro-atherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of LTB4 and LPS. An orbital shaker was used to expose the endothelial cells to oscillatory shear in culture dishes, and Computational fluid dynamics (CFD) was applied to quantify the shear stress on the bottom of the orbiting dish. Directionality of oscillatory shear was characterized by a newly developed hemodynamic parameter — Directional oscillatory shear index (DOSI), which was demonstrated in a previous study to significantly impact cell morphology (4). Results showed that DOSI significantly altered gene expression. Therefore, directionality of shear modulates atherosclerotic gene expression in vitro and thus, may influence the formation of atherosclerotic plaque in vivo.

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Non-redundant inhibitor of differentiation (Id) gene expression and function in human prostate epithelial cells

The Prostate ◽

10.1002/pros.20366 ◽

2006 ◽

Vol 66 (9) ◽

pp. 921-935 ◽

Cited By ~ 31

Author(s):

Ananthi J. Asirvatham ◽

Michelle A. Schmidt ◽

Jaideep Chaudhary

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Human Prostate ◽

Prostate Epithelial Cells ◽

And Function

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Evaluation of Antibiotic Tolerance in Pseudomonas aeruginosa for Aminoglycosides and its Prediction of Resistance Development Through In-silico Transcriptomic Analysis

10.1101/2021.05.01.442230 ◽

2021 ◽

Author(s):

Abishek Kumar B ◽

Bency Thankappan ◽

Angayarkanni Jayaraman ◽

Akshita Gupta

Keyword(s):

Gene Expression ◽

Pseudomonas Aeruginosa ◽

Gene Expressions ◽

Resistance Development ◽

Adaptive Resistance ◽

Antibiotic Response ◽

Secretory System ◽

Kinetics Of ◽

Alginate Biosynthesis

Pseudomonas aeruginosa causes severe life-threatening infections and are difficult to treat. The lack of antibiotic response in P. aeruginosa is due to adaptive resistance, which prevents the entry of antibiotics into cytosol of the cell. Among different groups of antibiotics, aminoglycosides show superior antibiotic response and are used as a parental antibiotic for treatment. This study aims to determine the kinetics of adaptive resistance development and gene expression changes in P. aeruginosa exposed to amikacin, gentamicin, and tobramycin. In vitro antibiotic exposure to P. aeruginosa was performed and optical density of the cells were monitored for every 12 hours until 72 hours. The growth pattern plotted in graph represents the kinetics of adaptive resistance developed to respective antibiotics. The transcriptomic profile of P. aeruginosa PA14 to post exposed antibiotic was taken from Gene Expression Omnibus (GEO), NCBI. The gene expressions of two datasets were analyzed by case-control study. Tobramycin exposed P. aeruginosa failed to develop adaptive resistance in 0.5ug/mL, 1ug/mL and 1.5ug/mL of its MIC. Whereas, amikacin and gentamicin treated P. aeruginosa developed tolerance in the inhibitory concentrations of the antibiotics. This depicts the superior in vitro response of tobramycin over the gentamicin and amikacin. Furthermore, tobramycin treated P. aeruginosa microarray analysis resulted in low expression of catalytic enzyme 16s rRNA Methyltransferase E, B & L, alginate biosynthesis genes and several proteins of Type 2 Secretory System (T2SS) and Type 3 Secretory System (T3SS). The Differentially Expressed Genes (DEGs) of alginate biosynthesis, and RNA Methyltransferases suggests increased antibiotic response and low probability of developing resistance. The use of tobramycin as a parental antibiotic with its synergistic combination might combat P. aeruginosa with increased response.

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MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans

eLife ◽

10.7554/elife.53600 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Calvin VanOpstall ◽

Srikanth Perike ◽

Hannah Brechka ◽

Marc Gillard ◽

Sophia Lamperis ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Treatment Strategies ◽

Human Prostate ◽

Protein Activity ◽

Prostate Epithelial Cells ◽

New Treatment ◽

Hox Protein

The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13. Integration of ChIP-seq and RNA-seq data revealed direct and HOXB13-dependent regulation of proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression. These results define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing prostate cancer progression and provide a mechanistic framework for the investigation of HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.

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