RESUMO
BACKGROUND: Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele. METHODS: Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA. RESULTS: Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients. CONCLUSION: This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.
Assuntos
Fragmentação do DNA , Infertilidade Masculina , MicroRNAs , Proteína 1 Homóloga a MutL , Estresse Oxidativo , Espermatozoides , Varicocele , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Varicocele/genética , Varicocele/metabolismo , Varicocele/patologia , Estresse Oxidativo/genética , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Espermatozoides/metabolismo , Adulto , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Sêmen/metabolismo , Motilidade dos Espermatozoides/genética , Antioxidantes/metabolismoRESUMO
There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especially platelet/lymphocyte ratio which may be an independent predictor of prognosis in patients with RCC and other forms of cancer. Via in silico analysis upon RCC-specific deleted genes in chromosome 3, four possible ceRNAs (ATXN3, ABI2, GOLGB1 and SMAD2) were identified. Then, the expression levels of these genes in tumour and adjacent healthy kidney tissues of 19 RCC patients were determined by real-time PCR. ATXN3 and GOLGB1 gene expression levels increased but ABI2 gene expression level decreased in tumour kidney tissues when compared to normal ones. ATXN3, ABI2 and GOLGB1 gene expression levels were significantly higher in Fuhrman grade 4 than other grades (P < .001). ABI2 gene expression levels were significantly associated with higher platelet/lymphocyte ratio of the patients with RCC (P < .05). ATXN3, ABI2 and GOLGB1 may predict higher RCC grades. Also, ABI2 may regulate platelet/lymphocyte ratio which may be an independent predictor of RCC and other forms of cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Plaquetas , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Linfócitos , MicroRNAs/genética , Idoso , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Projetos Piloto , Contagem de PlaquetasRESUMO
Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients.
Assuntos
Processamento Alternativo , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Regulação para Cima , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
Background/aim: This study aimed to comparatively analyze the expression levels of the SLC1A1 gene in renal specimens from tumors and adjacent healthy kidney tissues of patients with clear cell renal cell carcinoma (ccRCC). Materials and methods: Nineteen patients diagnosed with ccRCC were included in the study. The expression levels of the SLC1A1 and GAPDH genes were measured in tumor and formalin-fixed paraffin-embedded (FFPE) tissue specimens from the adjacent healthy kidney of each subject. Via the GEPIA database, the distribution of SLC1A1 gene expressions in ccRCC and healthy kidney tissues was obtained. The relative expression of SLC1A1 was evaluated for the association with the clinical parameters of the patients. Results: The expression of the SLC1A1 gene was significantly higher in males than females (P = 0.029). Also, there were statistically significant associations between stages IIIV and Fuhrman grades 24 with respect to SLC1A1 gene expression (P < 0.001 for both). Moreover, low levels of red blood cell and hemoglobin counts were significantly associated with the SLC1A1 expression (P < 0.001 and P = 0.005, respectively). The expression of the SLC1A1 gene in tumor tissues increased approximately 3 times compared with normal kidney tissues (P < 0.05). According to the GEPIA database, SLC1A1 gene expression is significantly higher in ccRCC patients than healthy persons (P = 0.01). Conclusion: The change in the expression of SLC1A1 may be crucial for ccRCC pathophysiology.
Assuntos
Carcinoma de Células Renais/genética , Transportador 3 de Aminoácido Excitatório/genética , Neoplasias Renais/genética , Adulto , Análise de Variância , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
CONTEXT: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children. MicroRNAs (miRNA) are small RNAs which have regulatory functions in many biological processes. OBJECTIVE: We aimed to determine miRNA expression levels in plasma of children with DCM. MATERIALS AND METHODS: Plasma expression levels of 379 miRNAs were compared between 23 DCM and 26 healthy children. RESULTS: The expression levels of miR-618, miR-875-3p, miR-205, miR-194, miR-302a, miR-147, and miR-544 were found decreased. The expression levels of miR-518f and miR-454 were found increased in DCM patients. DISCUSSION: miRNA level differences may provide the chance of using these miRNAs as new biomarkers.
Assuntos
Cardiomiopatia Dilatada/sangue , Adolescente , Biomarcadores/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Perfilação da Expressão Gênica , Humanos , Lactente , MicroRNAs/sangue , TranscriptomaRESUMO
BACKGROUND: Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). METHODS: One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. RESULTS: Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (ß = 0.508, p = 0.001). CONCLUSION: Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.
Assuntos
Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único , Urotensinas/sangue , Urotensinas/genética , Adulto , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Adulto JovemRESUMO
Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics. Graphical Abstract Multiple RNA transcripts have common MREs for the similar miRNA in their 3'-untranslated regions (3'-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers-the name for ceRNAs taking crucial roles in oncogenic pathways-are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.
Assuntos
MicroRNAs/fisiologia , Neoplasias/genética , Animais , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/metabolismo , Oncogenes , RNA Longo não Codificante/fisiologiaRESUMO
MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.
Assuntos
Proteínas ADAM/genética , Secretases da Proteína Precursora do Amiloide/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , MicroRNAs/genética , Interferência de RNA , RNA Mensageiro/genética , Regiões 3' não Traduzidas , Proteína ADAM10 , Adulto , Idoso , Sequência de Bases , Sítios de Ligação , Biomarcadores Tumorais , Neoplasias da Mama/cirurgia , Feminino , Humanos , MicroRNAs/química , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/químicaRESUMO
Sagliker syndrome (SS) develops particularly before puberty while chronic kidney disease (CKD) reaches stage 3 with overt secondary hyperparathyroidism. We conducted screening for mutations in all the 13 exons of GNAS1 gene, all 3 exons of FGF23, and all 18 exons in FGFR3 genes in 23 patients. In 73.9% (17 of 23) patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and 3 nonsense. Mismutations were in different manner. There were also 6 heterozygous transversion polymorphisms in exons. Six were introngenic mutations (introns 65626, 70387, 70817). We found 10 mutations with different manner in FGF23 gene. Two were defined previously but remaining 8 were novel mutations. Three were in intronic region near exon 2. We sequenced all exons and intronic regions near exon-exon junction regions of FGFR3 gene. We found 22 mutations with different manner. Six were defined previously and remaining 16 were novel mutations. Eight of them were in intronic region near exon 11 and the last 2 were in noncoding exonic region of exons. One was in the exon-exon junction region between exon 11 and 12, therefore this mutation might be preventing splicing of this intron. Because the incidence of CKD late stage 3 is around 8% but the incidence of SS is around 0.5% in CKD, these gene mismutations might be responsible for bone deformities such as McCune-Albright syndrome and achondroplasias. Although our patients were not resembling any of them, they could be in between, and SS might be a combination-compulsion of bone dysplasias-hereditary osteodystrophies and CKD.
Assuntos
Anormalidades Múltiplas/genética , Anormalidades Craniofaciais/genética , Hiperparatireoidismo Secundário/genética , Mutação de Sentido Incorreto/genética , Insuficiência Renal Crônica/genética , Criança , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , SíndromeRESUMO
It is known that high-dose radiation has an effect on tissue healing, but tissue healing does not occur when low dose radiation is applied. To clarify this issue, we compare the treatment success of low dose radiation with programmed cell death mechanisms on wounded tissue. In this study, we aimed to investigate the interactions of low and high-dose radiation using an autophagic mechanism. We included 35 adult Wistar-Albino rats in this study. All animals were injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tips of 18-gauge needles were used to develop a superficial scratching on the left cheek pouch mucosa by dragging in a linear movement on third and fifth days. After mucositis formation was clinically detected, animals were divided into five groups (n = 7). Different wavelengths of laser irradiations (1064 nm, Fidelis Plus, Fotona, Slovenia; 980 nm, FOX laser, A.R.C., Germany; 810 nm, Fotona XD, Fotona, Slovenia; 660 nm, HELBO, Medizintechnik GmbH, Wels, Austria) were performed on four groups once daily for 4 days. The laser irradiation was not performed on the control group. To get the tissue from the left cheek at the end of fourth day from all animals, oval excisional biopsy was performed. Molecular analysis assessments of pathological and normal tissue taken were performed. For this purpose, the expression analysis of autophagy genes was performed. The results were evaluated by normalization and statistics analysis. We found that Ulk1, Beclin1, and Atg5 expression levels were increased in the rats when the Nd:YAG laser was applied. This increase showed that a 1064-nm laser is needed to activate the autophagic mechanism. However, in the diode applications, we found that Beclin1, Atg10, Atg5, and Atg7 expressions numerically decreased. Atg5 is responsible for the elongation of autophagosome. Becn1 is a control gene in the control mechanism of autophagy. The reduction of the expression of these genes leads us to think that it may depend on the effect of drug (5-FU) used to form model. Expressions of therapeutic genes increase to ensure hemostasis, but in our study, expressions were found to decrease. More detailed studies are needed.
Assuntos
Autofagia/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Terapia com Luz de Baixa Intensidade , Mucosite/radioterapia , Animais , Masculino , Mucosa Bucal/efeitos da radiação , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.
Assuntos
Neoplasias Colorretais/genética , Expressão Gênica , MicroRNAs/genética , Idoso , Autofagia/genética , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de NeoplasiasRESUMO
HER2/ErbB2, a known proto-oncogene (also known as HER2, neu), is among the most practiced molecules in the cancer area. Human epidermal growth factor receptor 2 (HER2) is over expressed in approximately 20-30 % of breast cancer tumors and also in a lot of other human cancer types. It is known to be related to the aggressiveness of the disease, increased mortality and higher relapse ratio. The unusual HER2 overexpression is associated with more severe disease characteristics in several cancers. In recent past, there have been remarkable advances in understanding the role of the HER2 gene in cancers. Caspases are well renowned proteases that act as essential initiators and executioners of the apoptotic process. The primary function of HER2 is suppressing apoptosis to enhance cell survival and eventually giving rise to uncontrolled proliferation and tumor growth. The objective of this work was to study the expression levels of HER2 and apoptosis related factors CASP-3 and CASP-8 in several breast and other cancer cell lines and finally to find a meaningful correlation between all these. We summed up by obtaining an increase in expression of HER2 in all cancer cell lines as compared to that of CASP-3 and CASP-8. In summary we conclude that HER2 promotes cell survival by inhibiting apoptosis i.e. by downregulating CASP-3 and CASP-8. This is a novel study comprising the expression study of HER2 and different caspases in different cancer cell lines simultaneously. It is thus expected that this study will aid in better establishment of correlation between HER2 and caspases in different malignancies.
Assuntos
Apoptose/genética , Caspase 3/genética , Caspase 8/genética , Neoplasias/metabolismo , Receptor ErbB-2/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/genética , Proto-Oncogene MasRESUMO
Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 -675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66%, respectively. No mutation was detected in 92 (1.95%) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.
Assuntos
Doenças Cardiovasculares/genética , Fator V/genética , Fator XIII/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Protrombina/genética , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , TurquiaRESUMO
Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 249100), particularly common in populations of Mediterranean extraction. MEFV gene, responsible for FMF, encoding pyrin has recently been mapped to chromosome 16p13.3. In the present study, 3,341 unrelated patients with the suspicion of FMF in south-east part of Turkey between the years 2009 and 2013 were enrolled and genomic sequences of exon 2 and exon 10 of the MEFV gene were scanned for mutations by direct sequencing. We identified 43 different type of mutations and 9 of them were novel. DNA was amplified by PCR and subjected to direct sequencing for the detection of MEFV gene mutations. Among the 3,341 patients, 1,598 (47.8 %) were males and 1,743 (52.1 %) were females. The mutations were heterozygous in 806 (62.3 %), compound heterozygous in 188 (14.5 %), homozygous in 281 (21.8 %) and mutations had complex genotype in 17 (1.32 %) patients. No mutation was detected in 2,051 (61.4 %) patients. The most frequent mutations were M694V, E148Q, M680I(G/C) and V726A. We could not find any significant differences between the two common mutations according to the gender. Molecular diagnosis of MEFV is a useful tool in clinical practice, thus a future study relating to genotype/phenotype correlation of FMF in more and larger group in Turkish population involving the whole MEFV gene mutations is necessary.
Assuntos
Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Testes Genéticos , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Turquia , Adulto JovemRESUMO
Caspases are important initiators and most well-known finishers of apoptosis. By changing the death propagation homeostatic equilibrium, their different expression patterns might trigger the progression of hazardous diseases like cancer. miR-221 is an oncogenic miRNA. It is known to have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also tried to establish a prominent relationship between miR-221 and its role in apoptosis by studying their expression levels. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3.
Assuntos
Caspase 3/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Apoptose , Caspase 3/genética , Linhagem Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , MicroRNAs/genética , Regulação para CimaRESUMO
Male infertility is a multifactorial heterogeneous reproductive disorder in which genetic, epigenetic, and environmental factors play a role in the development of disease. Recent studies have shown that retrotransposon expression alterations may be related to impairment of spermatogenesis. Therefore, in this pilot study, we aimed to investigate whether HERV-K6 and HERV-K11 insertional variations have a role in idiopathic infertility among normozoospermic men. Genomic DNA isolated from the blood samples of 41 infertile normozoospermic and 45 fertile normozoospermic men were analyzed by inter-retrotransposon polymorphism polymerase chain reaction. HERV-K6 variation rates in the infertile and the fertile group were 0-58.3% and 0-53.4%, respectively. The variation rates of HERV-K11 were 0-75.0% in infertile and 0-77.8% in fertile men. The HERV-K6 and HERV-K11 insertion rates of the fertile group were higher than the infertile group (P < 0.0001 and P = 0.007, respectively). The findings of the study suggest that HERV-K6 and HERV-K11 retrotransposon insertion show variation among individuals, and their insertions might be associated with male infertility.
Assuntos
Infertilidade Masculina , Retroelementos , Humanos , Masculino , Projetos Piloto , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Fertilidade/genética , Espermatogênese/genéticaRESUMO
Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.
Assuntos
Apoptose , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Animais , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genéticaRESUMO
COVID-19 is a viral respiratory infection induced by the newly discovered coronavirus SARS-CoV-2. miRNA is an example of a strong and direct regulator of a gene's transcriptional activity. The interaction between miRNAs and their target molecules is responsible for homeostasis. Virus-derived and host-derived miRNAs are involved in the activity of hiding from immune system cells, inducing the inflammatory reaction through interplay with associated genes, during SARS-COV-2 infection. Interest in miRNAs has raised the comprehension of the machinery and pathophysiology of SARS-COV-2 infection. In this review, the effects and biological roles of miRNAs on SARS-CoV-2 pathogenicity and life cycle are described. The therapeutic potential of miRNAs against SARS-CoV-2 infection are also mentioned.
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COVID-19 , MicroRNAs , Humanos , MicroRNAs/genética , COVID-19/genética , SARS-CoV-2/genética , InflamaçãoRESUMO
BACKGROUND: C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases. Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular complex composed of Fyn, Plcγ1, and Sam68. Imatinib blocks the activity of full-length c-KIT but has no effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show tr-KIT overexpression. miR-128/193a- 5p/494 are miRNAs targeting FYN, PLCγ1, and SAM68 combinatorially. The study's question is: can miR-128/193a- 5p/494 be related to imatinib resistance in PCa? METHODS: LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration, RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT specific pathway elements and miR-128/193a-5p/494 were analyzed before and after imatinib administration. RESULTS: After imatinib administration, miR-128/193a-5p/494 were significantly overexpressed in LNCaP cells while downregulated significantly in PC3 cells (p<0.05). Also, FYN was upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration. CONCLUSION: Especially upregulation of FYN may sponge miR128/193a-5p/494 and downregulate their transcriptional activity in LNCaP cells having tr-KIT activity. So, miR-128/193a-5p/494 may have a critical role in imatinib resistance via a tr-KIT pathway.
Assuntos
MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Mesilato de Imatinib/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Regulação para Cima , Regiões Promotoras GenéticasRESUMO
PURPOSE: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis. METHODS: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified. RESULTS: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively. CONCLUSION: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition.