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MicroRNAs are key regulators of various fundamental biological processes and, although representing only a small portion of the genome, they regulate a much larger population of target genes. Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. MicroRNA targeting is mostly achieved through specific base-pairing interactions between the 5' end ('seed' region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR diminish mRNA stability. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. Calin and Croce were the first to demonstrate a connection between microRNAs and increased risk of developing cancer, and meanwhile the role of microRNAs in carcinogenesis has definitively been evidenced. It needs to be considered that the complex mechanism of gene regulation by microRNAs is profoundly influenced by variation in gene sequence (polymorphisms) of the target sites. Thus, individual variability could cause patients to present differential risks regarding several diseases. Aiming to provide a critical overview of miRNA dysregulation in cancer, this article reviews the growing number of studies that have shown the importance of these small molecules and how these microRNAs can affect or be affected by genetic and epigenetic mechanisms.
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OBJECTIVE: To investigate the prevalence of the p27 gene polymorphism in women with endometriosis. STUDY DESIGN: Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population. RESULTS: We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p=0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR=1.9; 95% CI, 1.120-3.343). CONCLUSION: The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.
Assuntos
Inibidor de Quinase Dependente de Ciclina p27/genética , Endometriose/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: The purpose of this study was to investigate Vascular Endothelial Growth Factor Expression (VEGF) gene regulation by isoflavone in urinary tract tissues of castrated adult rats. DESIGN: Forty-five adult rats, 90 days old, weighting 200 g were used, receiving a soy-free ration. The animals were castrated for drug administration for 30 days (125 microg genisteine/g body weight/day) and sacrificed, divided into three groups: Group I-control; Group II-started isoflavone administration on the 5th day after castration; Group III-started isoflavone administration on the 28th day after castration. RNA was isolated from each bladder and urethra. Determination of VEGF gene regulated by isoflavone was obtained using a semiquantitative RT-PCR and immunohistochemistry of total RNA isolated from bladder and urethra. RESULTS: Our results demonstrate that isoflavone was able to upregulate mRNA level of the VEGF gene in the lower urinary tract of rats in Group II, where isoflavone administration was started at an early phase of estrogen deprivation, while in Group III, where isoflavone administration was started in the late phase of hypoestrogenism, did not show alteration of bladder and urethra VEGF gene expression, compared to placebo, maintaining the same level of the castrated rats without treatment. CONCLUSIONS: The data indicate that VEGF expression in rats is also regulated by isoflavone in early phase of hypoestrogenism.
Assuntos
Estrogênios/deficiência , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Sistema Urinário/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Feminino , Expressão Gênica/efeitos dos fármacos , Ovariectomia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sistema Urinário/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
OBJECTIVE: To evaluate the association of intron 1 and exon 1 polymorphisms in the estrogen receptor alpha gene (ER-alpha) with endometriosis in women. DESIGN: Association study. SETTING: Endometriosis Unit, Federal University of São Paulo. PATIENT(S): The control group consisted of volunteers older than 45 years who had no evidence of endometriosis antecedents. Two groups with the disease were evaluated: the first group had stage I or II endometriosis and the second group stage III or IV. INTERVENTION(S): Polymerase chain reaction (PCR) followed by digestion with HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1 polymorphisms, respectively, in a total of 125 controls and 105 affected women. MAIN OUTCOME MEASURE(S): Frequency and distribution of HaeIII and MspI polymorphisms in ER-alpha. RESULT(S): No significant differences in the frequency of polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis patients were compared with control subjects. Furthermore, the frequency of ER-alpha polymorphisms within the two different groups of patients with disease was statistically similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms (SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and endometriosis was 0.976. CONCLUSION(S): The evaluated polymorphisms were not associated with endometriosis.
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Endometriose/genética , Receptor alfa de Estrogênio/genética , Éxons , Íntrons , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Razão de Chances , Medição de RiscoRESUMO
OBJECTIVES: In this study, the authors analyzed the immunoexpression of p16 in high-risk human papillomavirus DNA-negative normal and nonneoplastic cervical epithelia, in low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, and squamous cell carcinoma. MATERIALS AND METHODS: A retrospective study, in which 58 normal cervical hysterectomy samples, 56 nonneoplastic cervical biopsies, 88 CIN 1, 33 CIN 2, 32 CIN 3, and 47 invasive squamous cell carcinoma biopsies, were evaluated for p16 immunoexpression. Human papillomavirus tests were also performed. RESULTS: p16 immunohistochemistry seems to reveal possible different biological subgroups of lesions among morphologically similar mildly dysplastic cervical epithelia. CONCLUSION: Distribution patterns of p16 protein might be useful to predict different outcomes in CIN 1.
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Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Inibidor p16 de Quinase Dependente de Ciclina/análise , Displasia do Colo do Útero/química , Neoplasias do Colo do Útero/química , Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colo do Útero/química , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , DNA Viral/análise , Células Epiteliais/química , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Due to the conflicting results regarding the association between breast cancer and the GSTM1 null mutation, our aim was to research this association in a Brazilian population and correlations with smoking, reproductive history and several clinical pathologies. A case-control study was performed on 105 women with breast cancer and 278 controls. Extraction of DNA was accomplished according to the protocol of the GFX kit and polymorphism analysis by the PCR technique. The control and experimental groups were compared and statistical analysis assessed by X2 or Fisher's exact test. The deletion in the GSTM1 gene in the breast cancer group had a prevalence of 32 (30.4%) individuals with the presence of null mutation. In the control group, the null mutation was present in 104 (37.4%) women. Upon comparison of the two groups, no statistically significant difference of the GSTM1 gene was observed, with an odds ratio (OR) of 0.74, 95%, confidence interval (CI) 0.45 - 1.20, p = 0.277. The results conclusively show that single gene GSTM1 polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, in this study no correlation was found between GSTs and smoking, reproductive history and several clinical pathologies with respect to cancer risk.
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Neoplasias da Mama/genética , Glutationa Transferase/genética , Polimorfismo Genético , História Reprodutiva , Adulto , Estudos de Casos e Controles , Feminino , Deleção de Genes , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversosRESUMO
Due to the conflicting results regarding the association between breast cancerand the GSTM1 null mutation, our aim was to research this associationin a Brazilian population and correlations withsmoking, reproductive history and several clinical pathologies. A case-control study was performed on 105 women with breast cancer and 278 controls. Extraction of DNA was accomplished according to the protocol of the GFX© kit and polymorphism analysis by the PCR technique. The control and experimental groups were compared and statistical analysis assessed by Xy or Fisher's exact test. The deletion in the GSTM1 gene in the breast cancer group had a prevalence of 32 (30.4 percent) individuals with the presence of null mutation. In the control group, the null mutation was present in 104 (37.4 percent) women. Upon comparison of the two groups, no statistically significant difference of the GSTM1 gene was observed, with an odds ratio (OR) of 0.74, 95 percent, confidence interval (CI) 0.45 - 1.20, p = 0.277. The results conclusively show that singlegene GSTM1 polymorphisms do not confer a substantial risk of breastcancer to its carriers. Furthermore, in this study no correlation was found between GSTs andsmoking, reproductive history and several clinical pathologies with respect to cancer risk.