Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.

Download Full-text

Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen-induced retinopathy

Pediatric Research ◽

10.1038/s41390-019-0598-y ◽

2019 ◽

Vol 87 (3) ◽

pp. 485-493 ◽

Cited By ~ 1

Author(s):

Magdalena Zasada ◽

Anna Madetko-Talowska ◽

Cecilie Revhaug ◽

Anne Gro W. Rognlien ◽

Lars O. Baumbusch ◽

...

Keyword(s):

Gene Expression ◽

Mononuclear Cells ◽

Expression Patterns ◽

Control Group ◽

Global Pattern ◽

Retinal Cells ◽

Altered Expression ◽

Oxygen Induced Retinopathy ◽

Blood Mononuclear Cells ◽

Long Term Impact

Abstract Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Download Full-text

Equine Hoof Canker: Bovine Papillomavirus Infection Is Not Associated With Impaired Keratinocyte Differentiation

Veterinary Pathology ◽

10.1177/0300985820921820 ◽

2020 ◽

Vol 57 (4) ◽

pp. 525-534

Author(s):

Veronika Apprich ◽

Theresia Licka ◽

Sabrina Freiler ◽

Cordula Gabriel

Keyword(s):

Adhesion Molecules ◽

Intermediate Filaments ◽

Expression Patterns ◽

Keratinocyte Differentiation ◽

Bovine Papillomavirus ◽

Tissue Samples ◽

Altered Expression ◽

Morphological Alterations ◽

Papillomavirus Infection ◽

Equine Hoof

Impaired keratinocyte differentiation has recently been suggested as a key event in equine hoof canker development. Koilocytotic appearance of keratinocytes, one of the most characteristic morphological alterations in hoof canker tissue, is also a common marker for papillomavirus (PV) infection, and bovine PV-1 and/or -2 (BPV-1/2) has previously been detected in equine canker patients. Therefore, the present study aimed to correlate the frequency and severity of koilocytotic keratinocytes with BPV detection in hoof canker samples. Hoof tissue of 5/18 canker-affected horses and 2/6 control horses tested positive for BPV-1/2 DNA using polymerase chain reaction. Thus, no association between the presence of BPV-1/2 papillomaviral DNA and koilocytotic appearance was found. Proteins associated with but not specific for PV infection were also investigated. Using immunohistochemistry, specific adhesion molecules (E-cadherin and β-catenin) and intermediate filaments (keratins 6 and 14) important for intact epidermal barrier function and keratinocyte differentiation were documented in control samples ( n = 6) and in hoof canker tissue samples ( n = 19). Altered expression patterns of intermediate filaments and adhesion molecules were demonstrated in canker tissue, confirming the importance of incomplete keratinocyte differentiation, as well as the crucial role of keratinocyte differentiation in hoof canker.

Download Full-text

NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.616220 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xinzhuan Jia ◽

Lan Wei ◽

Zhengmao Zhang

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cell Apoptosis ◽

Expression Patterns ◽

Chemotherapy Resistance ◽

Direct Interaction ◽

Luciferase Reporter ◽

Tissue Samples ◽

Qrt Pcr

BackgroundAccumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.PurposeOur aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.MethodsThe expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and SOX3. Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.ResultsIn this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed in vivo. Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted SOX3 mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.ConclusionNEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/SOX3 pathway, showing that NEAT1 might be a potential target for OC resistance treatment.

Download Full-text

EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer

Cancer Cell International ◽

10.1186/s12935-020-01622-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Dongbo Wu ◽

Fanglan Wu ◽

Birong Li ◽

Wei Huang ◽

Donglian Wang

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Expression Pattern ◽

Transforming Growth Factor Beta ◽

Promoter Methylation ◽

Transforming Growth Factor ◽

Expression Patterns ◽

Luciferase Reporter ◽

Altered Expression ◽

Gene Assay

Abstract Background It has been known that ovarian cancer (OC) is a leading cause for women mortality globally. We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. Methods High expression patterns of EZH2 and miR-139 and low LPA1 expression pattern in OC were evaluated using RT-qPCR and immunoblotting, while their correlation was assessed by the Spearman’s rank and Pearson’s correlation coefficient. Subsequently, dual-luciferase reporter gene assay was applied to validate the binding relationship between miR-139 and LPA1, while H3K27me enrichment was assessed by ChIP assay. After that, the effects of altered expression of EZH2, miR-194, or LPA1 on the cell biological functions and the expression pattern of TGF-related factors were evaluated. Results We found that EZH2 repressed the miR-139 expression pattern by recruiting H3K27me3 to promote miR-139 promoter methylation, while silencing of EZH2 suppressed in vitro cancer progression by increasing miR-139. LPA1 was a target of miR-139, and could activate the TGF-β signaling pathway, which hastened the OC progression. miR-139-targeted inhibition of LPA1 and LPA1-activated TGF-β signaling pathway were evidenced to be critical mechanisms underlying the effects of EZH2 on OC cells. Lastly, silencing of EZH2 inhibited the xenograft growth in vivo. Conclusions EZH2 could down-regulate miR-139 expression pattern by recruiting H3K27me3 to promote the miR-139 promoter methylation and activate the TGF-β pathway by up-regulating LPA1, which contributed to the progression of OC. The current study may possess potentials for OC treatment.

Download Full-text

Molecular Profiling Predicts the Existence of Two Functionally Distinct Classes of Ovarian Cancer Stroma

BioMed Research International ◽

10.1155/2013/846387 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Loukia N. Lili ◽

Lilya V. Matyunina ◽

L. DeEtte Walker ◽

Benedict B. Benigno ◽

John F. McDonald

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Expression Patterns ◽

Cancer Development ◽

Tissue Samples ◽

Cancer Stroma ◽

Expression Platform ◽

Gene Expression Platform ◽

Genes Encoding ◽

Ovarian Surface Epithelial

Although stromal cell signaling has been shown to play a significant role in the progression of many cancers, relatively little is known about its importance in modulating ovarian cancer development. The purpose of this study was to investigate the process of stroma activation in human ovarian cancer by molecular analysis of matched sets of cancer and surrounding stroma tissues. RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133 Plus 2.0) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of ovarian cancer patients (Cepi) and matched sets of surrounding cancer stroma (CS). For controls, ovarian surface epithelial cells (OSE) were isolated from the normal (noncancerous) ovaries and normal stroma (NS). Hierarchical clustering of the microarray data resulted in clear separations between the OSE, Cepi, NS, and CS samples. Expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples indicate the existence of two subgroups of cancer stroma (CS) with different propensities to support tumor growth. Our results indicate that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.

Download Full-text

The Molecular Analysis of rs11614913 Polymorphism from miRNA196a Gene and Its Relationship with TNF-α Gene Expression in Cervical Cancer

Jentashapir Journal of Cellular and Molecular Biology ◽

10.5812/jjcmb.101796 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Ahmad Hamta ◽

Fatemeh Hajihassani

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Malignant Tumors ◽

Control Group ◽

Tissue Samples ◽

Altered Expression ◽

Tnf Α ◽

Cancer Sample ◽

Rs11614913 Polymorphism ◽

Factor Α

Background: Cervical cancer (CC) is one of the most common malignant tumors in women, which has been diagnosed as fourth cancer in females worldwide. In addition to human papillomavirus (HPV), genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor α (TNF-α) gene, are involved in this cancer. Objectives: This study aimed to investigate the rs11614913 polymorphism from the miRNA196a gene and its association with the expression of the TNF-α gene in cervical cancer for early diagnosis and treatment. Methods: In this study, 52 samples of pre-cancerous and cancerous lesions, and 50 tissue samples were collected from healthy subjects in an Iranian population. DNA was extracted from the samples, and rs11614913 polymorphism of the miRNA196a gene was investigated by PCR. RNA was extracted from the samples, and the expression of the miRNA196a and TNF-α genes were evaluated. Finally, for data analysis, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used. Results: The frequency of CC, TC, and TT genotypes from rs11614913 polymorphism of miRNA196a gene was 0.58, 0.34, and 0.08, respectively, but in the healthy group it was 0.36, 0.46, and 0.18, respectively. The results also showed that the expression of miRNA196a and TNF-α genes in the patient group was higher than the control group. Conclusions: Based on the results of this study, a significant correlation was found between CC genotype and rs11614913 polymorphism of miRNA196a gene and TNF-α gene expression in the cervical cancer sample. Therefore, investigating these factors in patients with cervical cancer may be helpful.

Download Full-text

4D Doppler Ultrasound in High Grade Serous Ovarian Cancer Vascularity Evaluation—Preliminary Study

Diagnostics ◽

10.3390/diagnostics11040582 ◽

2021 ◽

Vol 11 (4) ◽

pp. 582

Author(s):

Marek Jerzy Kudla ◽

Michal Zikan ◽

Daniela Fischerova ◽

Mateusz Stolecki ◽

Juan Luis Alcazar

Keyword(s):

Ovarian Cancer ◽

Malignant Tumors ◽

Menopausal Status ◽

Power Doppler ◽

Serous Carcinoma ◽

Benign Tumors ◽

Control Group ◽

High Grade ◽

Tissue Samples ◽

4D Ultrasound

The aim of the study was to evaluate the usefulness of 4D Power Doppler tissue evaluation to discriminate between normal ovaries and ovarian cancer tumors. This was a prospective observational study. Twenty-three cases of surgically confirmed ovarian High Grade Serous Carcinoma (HGSC) were analyzed. The control group consisted of 23 healthy patients, each matching their study-group counterpart age wise (±3 years) and according to their menopausal status. Transvaginal Doppler 4D ultrasound scans were done on every patient and analyzed with 3D/4D software. Two 4D indices—volumetric Systolic/Diastolic Index (vS/D) and volumetric Pulsatility Index (vPI)—were calculated. To keep results standardized and due to technical limitations, virtual 1cc spherical tissue samples taken from the part with highest vascularization as detected by bi-directional Power Doppler were analyzed for both groups of ovaries. Values of volumetric S/D indices and volumetric PI indices were statistically lower in ovarian malignant tumors compared to normal ovaries: 1.096 vs. 1.794 and 0.092 vs. 0.558, respectively (p < 0.001). The 4D bi-directional Power Doppler vascular indices were statistically different between malignant tumors and normal ovaries. These findings could support the rationale for future studies for assessing this technology to discriminate between malignant and benign tumors.

Download Full-text

Phenotypic Resemblance to Neuropsychiatric Disorder and Altered mRNA Profiles in Cortex and Hippocampus Underlying IL15Rα Knockout

Frontiers in Neuroscience ◽

10.3389/fnins.2020.582279 ◽

2021 ◽

Vol 14 ◽

Author(s):

Yi He ◽

Yuxin Yu ◽

Yanan Li ◽

Weicheng Duan ◽

Zuoli Sun ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Development ◽

Expression Patterns ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Control Group ◽

Rna Seq ◽

Skeletal Muscle Development ◽

Altered Expression ◽

Y Maze

BackgroundPrevious studies of the functions of IL15Rα have been limited to immune activities and skeletal muscle development. Immunological factors have been identified as one of the multiple causes of psychosis, and neurological symptoms have been described in IL15Rα knockout (KO) mice. Seeking to explore possible mechanisms for this in the IL15Rα–/– mouse brain, we analyzed gene expression patterns in the cortex and hippocampus using the RNA-seq technique.MethodsIL15Rα KO mice were generated and littermate wildtype (WT) mice were used as a control group. A Y-maze was used to assess behavior differences between the two groups. The cortex and hippocampus of 3-month-old male mice were prepared and RNA-seq and transcriptome analysis were performed by gene set enrichment analysis (GSEA).ResultsCompared with the WT group, IL15Rα KO animals showed higher speed in the novel arm and more entrance frequency in the old arm in the Y-maze experiment. GSEA indicated that 18 pathways were downregulated and 13 pathways upregulated in both cortex and hippocampus from the GO, KEGG, and Hallmark gene sets. The downregulated pathways formed three clusters: respiratory chain and electron transport, regulation of steroid process, and skeletal muscle development.ConclusionIL15Rα KO mice exhibit altered expression of multiple pathways, which could affect many functions of the brain. Lipid biosynthesis and metabolism in the central nervous system (CNS) should be investigated to provide insights into the effect of IL15Rα on psychosis in this murine model.

Download Full-text

Protein Expression Patterns in ovarian cancer cells Associated with Monofunctional Platinums Treatment

10.1101/628958 ◽

2019 ◽

Cited By ~ 1

Author(s):

Laila Arzuman ◽

Mohammad Ali Moni ◽

Philip Beale ◽

Jun Q. Yu ◽

Mark Molloy ◽

...

Keyword(s):

Ovarian Cancer ◽

Patient Survival ◽

Expression Patterns ◽

Differentially Expressed ◽

Ovarian Cancer Cells ◽

Altered Expression ◽

Expression Levels ◽

Risk Of Death ◽

Platinum Based Chemotherapy ◽

Resistant Cells

ABSTRACTPlatinum drugs cisplatin and carboplatin, given in combination with paclitaxel, constitute the standard chemotherapy against ovarian cancer (OC). Oc chemoresistance is a major obstacle to effective treatment, but knowledge of the mechanisms that underlie it remains incomplete. We thus sought to discover key proteins associated with platinum resistance by comparing A2780 OC cells with A2780cisR cells (resistant cells derived from the A2780 line) to identify proteins with markedly altered expression levels in the resistant cells. We also determined which proteins in these cells had altered expression in response to treatment with either designed monofunctional platinum alone or a combination with cisplatin with selected phytochemical therapeutic agents.We thus performed proteomic analysis using 2D-gel electrophoresis A2780 and A2780cisR to identify proteins with differential expression; these were eluted and analysed by mass spectrometry to identify them. A total of 122 proteins were found to be differentially expressed between A2780 and A2780cisR cell lines in the absence of any drug treatment. Among them, levels of 27 proteins in A2780cisR cell line were further altered (up-or down-regulated) in response to one or more of the drug treatments. We then investigated primary OC tissue RNA expression levels (compared to l ovarian tissue) of genes coding for these candidate 27 proteins using publically available datasets (The Cancer Genome Atlas). We assessed how expression of these genes in OC tissue associates with patient survival using Cox Proportional Hazard (PH) regression models to determine relative risk of death associated with each factor. Our Cox PH regression-based machine learning method confirmed a significant relationship of mortality with altered expression of ARHGDIA, CCT6A and HISTIH4F genes. This indicated that these genes affect OC patient survival, i.e., provided mechanistic evidence, in addition to that of the clinical traits, that these genes may be critical mediators of the processes that underlie OC progression and mortality.Thus, we identified differentially expressed proteins that are implicated in platinum-based chemotherapy resistance mechanisms which may serve as resistance biomarkers. These drug resistance associated proteins may also serve as potential OC therapeutic targets whose blockade may enhance the effectiveness of platinum based drugs.

Download Full-text

Expression of miR-127, miR-154, and miR-183 in Medullary Thyroid Carcinoma Tumors

Iranian Journal of Public Health ◽

10.18502/ijph.v50i2.5358 ◽

2021 ◽

Author(s):

Mahsa RAHMANI SAMANI ◽

Marjan ZARIF-YEGANEH ◽

Atefeh MEHRABI ◽

Amir Nader EMAMI RAZAVI ◽

Sara SHEIKHOLESLAMI ◽

...

Keyword(s):

Thyroid Cancer ◽

Rna Extraction ◽

Control Group ◽

Tissue Samples ◽

Altered Expression ◽

Medullary Thyroid ◽

Formalin Fixed Paraffin ◽

Tumor Tissues ◽

Formalin Fixed Paraffin Embedded ◽

Ffpe Tissues

Background: Medullary thyroid cancer (MTC) accounts for 5%–10% of all thyroid cancers, but causes 13% of all thyroid cancer related deaths. MicroRNAs (miRs) have key functions in the development and progression of MTC. Altered expression of some miRs has been reported in many human cancers, including Thyroid cancer. Therefore, we aimed to analyze the expression of miR-154, miR-183 and miR-127 in MTC tumor tissues. Methods: In this case-control study, 15 MTC Formalin-fixed, paraffin-embedded (FFPE) tissue samples and 15 adjacent normal thyroid FFPE tissues, as a control group, were collected from Taleghani, and Loghman Hakim Hospitals, Tehran, Iran since 2005 till 2015. After RNA extraction and cDNA synthesis, the expression of miR127, miR-154 and miR-183 was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: Our data showed a significant increase in the expression of miR-127 in MTC samples in comparison with the control group (P<0.05). Although miR-154 and miR-183 expression levels had increase expression in MTC tumors, this change was not statistically significant. Conclusion: The miR-127 could be considered as a prognostic, diagnostic and therapeutic marker for the management of MTC, and it is proposed for further investigation to fully establish the role of this miRNA in MTC.

Download Full-text