ABSTRACT
Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells.
Subject(s)
Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/genetics , Hormones/pharmacology , MicroRNAs/genetics , Prostatic Neoplasms/pathology , Receptors, Somatomedin/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Receptor, IGF Type 1ABSTRACT
It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC).
Subject(s)
DNA Damage/genetics , DNA Damage/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , DNA Damage/drug effects , HeLa Cells , Humans , Mitomycin/toxicity , Nucleic Acid Synthesis Inhibitors/toxicity , RNA-Induced Silencing Complex/drug effects , RNA-Induced Silencing Complex/genetics , RNA-Induced Silencing Complex/metabolismABSTRACT
AIM: To identify markers for predicting aggressive forms of prostate cancer. MATERIALS AND METHODS: The study retrospectively evaluated expression of angiotensin II type 2 receptors (AT2-R) in prostate needle biopsy tissue from patients with and without biochemical recurrence after combined hormone and radiation therapy. RESULTS: The study findings showed that low expression of AT2-R in prostate tissue was associated with a high risk of biochemical recurrence. The data on the nature of AT2-R expression in prostate tissue of prostate cancer patients may be considered as a tool for predicting biochemical recurrence after combined hormone and radiation therapy. The test has a sensitivity of 87.5% and specificity of 85.71%.
Subject(s)
Biomarkers, Tumor/metabolism , Neoplasm Recurrence, Local/diagnosis , Prostate/metabolism , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Receptor, Angiotensin, Type 2/metabolism , Aged , Biomarkers, Tumor/analysis , Humans , Male , Prostate/chemistry , Receptor, Angiotensin, Type 2/analysisABSTRACT
The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment.
Subject(s)
DNA Methylation , Gene Expression Regulation/drug effects , MicroRNAs , Mitomycin/pharmacology , DNA Methylation/drug effects , DNA Methylation/genetics , HeLa Cells , Humans , MicroRNAs/biosynthesis , MicroRNAs/geneticsABSTRACT
The aim of the study was to analyze the role of the kallikrein-kinin and renin-angiotensin systems in the molecular mechanisms of prostate cancer (PCa) and use the findings for identification of new markers of the disease. Analysis of proteolytic disturbances in the prostatic secretions in benign prostatic hyperplasia (BPH) and prostate cancer based on the identification of key indicators of the kallikrein-kinin and renin-angiotensin system in the prostate secretion showed that kallikrein activity in prostate cancer is higher and the activity of angiotensin converting enzymes (ACE), by contrast, is lower than in BPH, apparently reflecting the reduction of angiotensin II and increase of the bradykinin content. A characteristic feature of prostate cancer is a dramatic increase in the inhibitory capacity of prostate secretion. It was found that in BPH patients, expression of B1 receptors in the prostate tissue is completely absent. The specific response with anti-B1 antibodies in the glandular epithelium was observed in malignant foci acini and prostatic intraepithelial neoplasia. In contrast, expression of the B2 receptors occurs in the stroma of both BPH and prostate cancer independent of stage and Gleason score. Indicators of kallikrein and ACE activity in prostate secretion and expression of the B1 receptors in prostate tissue may be utilized for prostate cancer diagnosis.
Subject(s)
Biomarkers, Tumor/metabolism , Kallikrein-Kinin System/physiology , Prostatic Hyperplasia/etiology , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/etiology , Prostatic Neoplasms/metabolism , Renin-Angiotensin System/physiology , Case-Control Studies , Humans , Immunohistochemistry , Male , Neoplasm GradingABSTRACT
Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissuie cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased arid decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was iegistered for all miRNAs withini the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, mil-30d-5p, and miR-204-5p) were identified, which, however, had never 'before been associated with coloreictal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with' coordinated aberrant expression as markers for colorectal cancer.
Subject(s)
Colonic Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Colonic Neoplasms/metabolism , Humans , MicroRNAs/metabolismABSTRACT
We identified 40 miRNAs with inherited aberrant expression by multiple parallel sequencing of human HeLa cells irradiated with X rays and mitomycin C. Twenty-two miRNAs were repressed and 15 miRNAs were induced after radiation and mytomycin C treatment. The expression of three miRNAs (miR-10b-5p, miR-148a-3p, and miR-340-5p) decreased after X-ray exposure and increased after mitomycin C treatment. The spectrum of aberrantly expressed miRNAs after X-ray and mitomycin C treatment is different, except for three miRNAs (mir-100-5p, miR-99b-5p, miR-501-3p), which showed the inherited decreased expression after both mutagens. It has been ascertained that for five miRNAs (miR-21-3p, miR-182-5p, miR-19b-3p, miR-30a-3p, and miR-30e-3p) with increased inherited expression, the targets are well-described tumor suppressor genes. For 9 miRNAs (miR-99b-5p, miR-148a-3p, miR-365a-3p, miR-193a-3p, miR-100-5p, miR-99a-5p, miR-29b-3p, miR-340-5p, and miR-23b-3p) with reduced inherited expression, the targets are oncogenes. The obtained results provide further support of the idea that induced epigenetic changes in the genome should be considered when assessing the long-term genetic effects of ionizing radiation and chemical compounds.
Subject(s)
Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , MicroRNAs/biosynthesis , Mitomycin/pharmacology , Nucleic Acid Synthesis Inhibitors/pharmacology , Gene Expression Regulation/genetics , HeLa Cells , Humans , MicroRNAs/genetics , X-RaysABSTRACT
Using affinity chromatography, two-dimensional electrophoresis, and MALDI-TOF mass spectrometry, plasminogen isoforms were separated and identified in blood plasma. Healthy donors and patients with prostate cancer in various stages of development were included in the studied sample. With the development of prostate cancer, four additional specific plasminogen isoforms are registered in blood plasma; they are characterized by lower molecular weights and higher pI values compared to isoforms found in the control group.
Subject(s)
Plasminogen/isolation & purification , Prostatic Neoplasms/blood , Aged , Humans , Male , Middle Aged , Plasminogen/analysis , Protein Isoforms/bloodSubject(s)
Plasminogen/chemistry , Prostatic Neoplasms/enzymology , Aged , Humans , Isoenzymes , Male , Middle Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosisSubject(s)
Cesium Radioisotopes/analysis , Geologic Sediments/analysis , Power Plants , Radiation Monitoring/methods , Radioactive Hazard Release , Animals , Arctic Regions , Ecosystem , Environmental Monitoring/methods , Fishes , Oceans and Seas , Radiometry/methods , Russia , Ships , Soil Pollutants, Radioactive/analysis , Water Pollutants, Radioactive/analysisABSTRACT
This work contributed to a joint research programme between the Finnish Centre for Radiation and Nuclear Safety and the Murmansk Marine Biological Institute in the Arctic. Radioanalyses for plutonium isotopes were performed on more than 50 sediment samples, 12 algae samples and 19 fish samples. Plutonium concentrations in algae and fish samples, including fish meat, bone and liver, were low or in many cases below detection limits. Some differences in plutonium concentrations of sediments were found between different sampling areas. However, the concentrations were low. The Pu isotopic ratios were similar to those found in environmental samples generally when Pu is derived from global fallout or discharges from reprocessing plants. No local enhancement of plutonium contamination was found in the marine areas studied. However, the sampling locations represent only areas of free access; prohibited military areas of North-west Russia with potential pollution sources were not included.
