scholarly journals Deregulated expression of selected histone methylases and demethylases in prostate carcinoma

2013 ◽  
Vol 21 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Filipa Quintela Vieira ◽  
Pedro Costa-Pinheiro ◽  
João Ramalho-Carvalho ◽  
Andreia Pereira ◽  
Francisco Duarte Menezes ◽  
...  
Keyword(s):  
Epigenetic Alterations ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Histone Methyltransferases ◽  
Expression Levels ◽  
Prostate Carcinogenesis ◽  
Localized Disease ◽  
Aggressive Tumors ◽  
Therapeutic Decision Making

Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR.SMYD3,SUV39H2,PRMT6,KDM5A, andKDM6Awere upregulated, whereasKMT2A-E (MLL1-5)andKDM4Bwere downregulated in PCa, compared with normal prostate tissues. Remarkably,PRMT6was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly,EZH2andSMYD3expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably,SMYD3expression levels were of independent prognostic value for the prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especiallySMYD3, might be of clinical usefulness for the assessment of PCa patients and assist in pre-therapeutic decision-making.

scholarly journals Differential Expression of Peroxisomal Proteins in Distinct Types of Parotid Gland Tumors

2021 ◽  
Vol 22 (15) ◽  
pp. 7872
Author(s):  
Malin Tordis Meyer ◽  
Christoph Watermann ◽  
Thomas Dreyer ◽  
Steffen Wagner ◽  
Claus Wittekindt ◽  
...  
Keyword(s):  
Redox Balance ◽  
Matrix Proteins ◽  
Parotid Tumor ◽  
Gene Expressions ◽  
Tissue Samples ◽  
Cellular Redox ◽  
Tumor Subtypes ◽  
Parotid Tumors ◽  
Aggressive Tumors

Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.

scholarly journals Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma

2021 ◽  
Author(s):  
Ridwan Dwi Saputro ◽  
Hanggoro Tri Rinonce ◽  
Yayuk Iramawasita ◽  
Muhammad Rasyid Ridho ◽  
Maria Fransiska Pudjohartono ◽  
...  
Keyword(s):  
Target Genes ◽  
Therapy Response ◽  
Mrna Levels ◽  
Independent Predictive Factor ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Nodular Melanoma ◽  
Expression Levels ◽  
Melanoma Tissue

Abstract Objective Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue and clinicopathologic characteristics and survival in Indonesian patients with primary nodular melanoma. Results Thirty-two tissue samples were analyzed. Upregulated PD-L1 was associated with shorter overall survival (hazard ratio: 2.930; 95% confidence interval: 1.011–8.489, p = 0.048) compared with patients with normoregulated PD-L1. A significant positive correlation was found between the expression levels of PD-L1 and NKG2A (rs: 0.768, p < 0.001). However, no clinicopathologic associations with PD-L1 and NKG2A mRNA levels were statistically proven. Comparison with other studies suggested that the choice of adjuvant therapy and the presence of TILs affect the prognostic role of PD-L1 expression. NKG2A was not proven to be an independent predictive factor but may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The combination of the mRNA levels of these two target genes may provide a novel prognostic and therapeutic direction for immunotherapy.

scholarly journals Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

2006 ◽  
Vol 13 (1) ◽  
pp. 151-167 ◽  
Author(s):  
Ta-Chun Yuan ◽  
Suresh Veeramani ◽  
Fen-Fen Lin ◽  
Dmitry Kondrikou ◽  
Stanislav Zelivianski ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Neuron Specific Enolase ◽  
Neuronal Morphology ◽  
Receptor Protein ◽  
Lncap Cells ◽  
Normal Prostate ◽  
Androgen Ablation ◽  
Prostate Carcinogenesis ◽  
Hormone Refractory

Neuroendocrine (NE) cells are the minor cell populations in normal prostate epithelial compartments. During prostate carcinogenesis, the number of NE cells in malignant lesions increases, correlating with its tumorigenicity and hormone-refractory growth. It is thus proposed that cancerous NE cells promote prostate cancer (PCa) cell progression and its androgen-independent proliferation, although the origin of the cancerous NE cells is not clear. To investigate the role of cancerous NE cells in prostate carcinogenesis, we characterized three NE subclone cell lines–NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated from androgen-sensitive human PCa LNCaP cells by culturing in an androgen-depleted environment, resembling clinical androgen-ablation therapy. These subclone cells acquire many features of NE cells seen in clinical prostate carcinomas, for example exhibiting a neuronal morphology and expressing multiple NE markers, including neuron-specific enolase, chromogranin B, neurotensin, parathyroid hormone-related peptide, and to a lesser degree for chromogranin A, while lacking androgen receptor (AR) or prostate specific antigen (PSA) expression. These cells represent terminally differentiated stable cells because after 3 months of re-culturing in a medium containing androgenic activity, they still retained the NE phenotype and expressed NE markers. Despite these NE cells having a slow growth rate, they readily developed xenograft tumors. Furthermore, media conditioned by these NE cells exhibited a stimulatory effect on proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions. Additionally, we found that receptor protein tyrosine phosphatase α plays a role in upregulating multiple NE markers and acquiring the NE phenotype. These NE cells thus represent cancerous NE cells and could serve as a useful cell model system for investigating the role of cancerous NE cells in hormone-refractory proliferation of PCa cells.

scholarly journals Analysis of the association between CDH2 gene polymorphism and osteoarthritis risk

2018 ◽  
Vol 34 ◽  
pp. 105-112 ◽  
Author(s):  
Guanglei Zhao ◽  
Jingsheng Shi ◽  
Jun Xia
Keyword(s):  
Gene Polymorphism ◽  
Chinese Population ◽  
Functional Score ◽  
Tissue Samples ◽  
Gender Stratification ◽  
Expression Levels ◽  
Study Population ◽  
Severity Of The Disease ◽  
And Control

Objective: to define the cadherin 2 (CDH2) gene polymorphism in Chinese osteoarthritis and control populations and to explore the correlation between CDH2 gene polymorphism and the risk of osteoarthritis. Method: a total of 476 patients with osteoarthritis were collected and 380 control subjects were included in the study. Clinical data such as gender, age and functional score were collected. The blood and tissue samples were collected and genotyped by PCR. Data analysis was performed using SPSS 19.0, Hapioview 4.2 and SNPstats softwares. Results: the association of rs11083271 and osteoarthritis was initially validated in this study population (P = 0.016, OR = 1.43 (1.07- 1.93)]. The risk of OA was significantly higher in heterozygous T/C than in homozygous T/T and C/C in rs11083271. By adjusting the age, according to gender stratification analysis, the heterozygous T/C genotype in rs11083271 significantly increased the risk of OA incidence in males [p = 0.011, 3.40 (1.55-7.43)]. The remaining rs sites were not significantly associated with OA. Notably, the association of rs11564299 with OA, regardless of genotyping, gene frequency and RNA expression levels in the study population, was not confirmed. Conclusion: in this study, we have analyzed the association between CDH2 gene polymorphism and OA in Chinese population. We found that rs11083271 heterozygous T/C genotype significantly increases the risk of OA and the severity of the disease. By contrast, the rs11564299 locus and OA have no significant correlation in the Chinese population. The role of rs11083271 in the regulation of CDH2 expression levels and the mechanisms by which it impacts OA remain to be further studied.

Bcl-2, p53, and Ki-67 expression in pterygium and normal conjunctiva and their relationship with pterygium recurrence

2020 ◽  
Vol 30 (6) ◽  
pp. 1232-1237
Author(s):  
Meydan Turan ◽  
Gulay Turan
Keyword(s):  
Recurrence Time ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
P53 Expression ◽  
Expression Levels ◽  
Significant Difference ◽  
Recurrent Pterygium ◽  
Primary Pterygium

Purpose: Pterygium is a common lesion of the ocular surface, and its etiology and pathogenesis are still uncertain. This study aimed to investigate the role of apoptosis and proliferation in pterygium formation and recurrence. Materials and methods: In this study, p53, Bcl-2, and Ki-67 expression levels were evaluated in primary pterygium ( n = 35) and recurrent pterygium ( n = 32) tissue samples and compared with normal conjunctiva ( n = 30) tissue samples. In addition, recurrent pterygiums were divided into three groups based on recurrence time, and their p53, Bcl-2, and Ki-67 expression levels were compared. Results: The results show that p53, Bcl-2, and Ki-67 expression levels were significantly higher in the pterygium tissue samples as compared to the control group ( p < 0.001, p < 0.001, and p < 0.001, respectively). When primary and recurrent pterygium tissues were compared, bcl-2 expression was higher in recurrent pterygium tissue samples ( p = 0.003). However, when Ki-67 and p53 expression levels were evaluated, no significant difference was found between primary and recurrent pterygium ( p = 0.215, p = 0.321, respectively). Also, p53 and Ki-67 expression were correlated in pterygium tissue samples, and Bcl-2 expression was significantly higher in pterygium that recurrence in the first 6 months after surgery. There was no difference between groups 1, 2, and 3 in terms of p53 and Ki-67 expression. Conclusion: Antiapoptotic mechanisms and proliferation play an important role in the etiopathogenesis of pterygium. Furthermore, Bcl-2 expression may be important in pterygium recurrence.

scholarly journals Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression and DNA Methylation Datasets

2021 ◽  
Vol 18 (16) ◽  
pp. 8697
Author(s):  
Federica Giambò ◽  
Gian Leone ◽  
Giuseppe Gattuso ◽  
Roberta Rizzo ◽  
Alessia Cosentino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pesticide Exposure ◽  
Methylation Status ◽  
Microrna Expression ◽  
Integrated Analysis ◽  
Epigenetic Alterations ◽  
Expression Levels ◽  
Prediction Tools

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

scholarly journals The role of long non-coding RNA (lncRNA) in the development of ovarian cancer

2020 ◽  
Vol 18 (2) ◽  
pp. e46-e56
Author(s):  
Dorota Gumiela ◽  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Tissue ◽  
Control Groups ◽  
Tissue Samples ◽  
Expression Levels ◽  
Lncrna Expression ◽  
Non Coding Rna ◽  
Metastatic Risk ◽  
Long Non Coding Rna

The aim of this study was to review research on the role of long non-coding RNA (lncRNA) in ovarian cancer. This article analyses studies on the effect of increased lncRNA expression on the size of ovarian cancer and the incidence of metastasis. The review covers a period from October 15, 2018 to August 22, 2020, and comprises 23 studies in which a total of 1,580 women with ovarian cancer participated, and an undetermined number of control groups where healthy tissue samples were collected. A review of the studies indicates that increased lncRNA expression is associated with elevated ovarian cancer size and metastatic risk. The most studied lncRNA include HOTAIR, CCAT2, GAS5, MALAT-1, UCA1. Studies assessing the expression levels of HOTAIR lncRNA and CCAT2 in normal and cancer tissue showed varying levels of expression in studies of different authors, which indicates that the expression of the same lncRNA may vary individually or is a result of study errors.

scholarly journals Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jaume Fores-Martos ◽  
Raimundo Cervera-Vidal ◽  
Julia Sierra-Roca ◽  
Carlos Lozano-Asencio ◽  
Vita Fedele ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Variable Number ◽  
Luminal A ◽  
Tissue Samples ◽  
Free Survival ◽  
Expression Levels ◽  
Cancer Subtypes ◽  
Increased Risk ◽  
Combined Data

AbstractPolymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97–1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10−12) but not in the rest of breast cancer subtypes.

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 Role of microRNA 4717, its effects on programmed cell death protein-1 in hepatitis B infection, and interaction between PDCD1 and miR-4717

2020 ◽  
Vol 18 ◽  
pp. 205873922093460
Author(s):  
Junhua Li ◽  
Andong Li
Keyword(s):  
Cell Death ◽  
Hepatitis B ◽  
Programmed Cell Death ◽  
Quantitative Polymerase Chain Reaction ◽  
Nucleotide Polymorphisms ◽  
Tissue Samples ◽  
Expression Levels ◽  
Si Rna ◽  
Cell Death Protein

It is suggested that programmed cell death protein-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma globally. This study was multi-aimed, that is, to investigate the role of microRNA (miR) 4717 and its target, PD-1 and to determine how the rs10204525 polymorphism in the 3′ untranslated region (3′UTR) of PD-1 affects its interaction with miR-4717. The expression levels of miR-4717 with various single-nucleotide polymorphisms were measured by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). A total of 54 tissue samples from HBV-infected individuals were collected, genotyped, and categorized into three groups; AA (n = 32), AG (n = 18), and GG (n = 4). The expression levels of gene PDCD1 and its corresponding PD-1 protein were significantly declined in the AA group as compared to AG and GG groups. There was a negative linear association between PDCD1 and miR-4717 in the tissue samples. HEPG2 cells transfected with an miR-4717 mimic or PD-1 small interfering (si)RNA exhibited significantly reduced expression levels of PDCD1 and PD-1, whereas cells transfected with an inhibitor of miR-4717 demonstrated greater expression levels of PDCD1 and PD-1 compared with the scramble control. In addition, cell viability and apoptosis were assessed in cells transfected with an miR-4717 mimic, PD-1 siRNA, or an miR-4717 inhibitor. Results revealed that treatment with the miR-4717 mimic or PD-1 siRNA enhanced viability of cells and reduced apoptosis. The results of this study suggest that rs10204525 polymorphism interferes with the interaction between PD-1 and miR-4717 and therefore induces apoptosis in liver cancer cells.

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