Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Nasofaringe/virologia , Pneumonia Viral/diagnóstico , Saliva/virologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Humanos , Pandemias , SARS-CoV-2 , Sensibilidade e Especificidade , Manejo de Espécimes , Fatores de TempoRESUMO
Mounting evidence indicates that deregulation of microRNAs (miRNAs) are involved in development of many human diseases, including cancers. Regulation of miRNA is a complicated process and some components in the regulation are known to be altered in human cancers. Among the miRNA regulation-related genes, we found that AGO1, AGO2, TNRC6A, TNRC6C, TARBP2 and EXPORTIN5 genes have mononucleotide repeats in their coding sequences. To see whether these genes are mutated in cancers with microsatellite instability (MSI), we analysed the mononucleotide repeats in 27 gastric cancers (GCs) with high MSI (MSI-H), 18 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 41 colorectal cancers (CRCs) with MSI-H, 14 CRCs with MSI-L and 45 CRCs with stable MSI (MSS) by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. We found AGO2, TNRC6A, TARBP2, TNRC6C and EXPORTIN5 mutations in 10, six, one, one and one cancer(s), respectively. They were detected in MSI-H but not in MSI-L or MSS cancers. The GCs and CRCs with MSI-H harboured one or more mutations of the genes in 22% and 27%, respectively. We also analysed Ago2 and TNRC6A protein expressions in GCs and CRCs with MSI-H. In cancers with MSI-H, loss of Ago2 expression was observed in 40% of GCs and 35% of CRCs, while loss of TNRC6A was observed in 52% of the GCs and 54% of the CRCs. Our data indicate that frameshift mutations in AGO2 and TNRC6A and their losses of expression are common in GCs and CRCs with MSI-H, and suggest that these alterations may contribute to the cancer development by deregulating miRNA regulation.
Assuntos
Autoantígenos/genética , Neoplasias Colorretais/genética , Fator de Iniciação 2 em Eucariotos/genética , Mutação da Fase de Leitura/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Proteínas Argonautas , Autoantígenos/metabolismo , Neoplasias Colorretais/patologia , Fator de Iniciação 2 em Eucariotos/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Carioferinas/genética , Instabilidade de Microssatélites , Proteínas de Ligação a RNA/genética , Análise de Sequência de DNA , Neoplasias Gástricas/patologiaRESUMO
Mounting evidence exists that alterations of ubiquitination processes are involved in cancer pathogenesis. Speckle-type POZ protein (SPOP) is a key adaptor for Cul3-based ubiquitination process. Recent studies reported that SPOP may be a tumor suppressor gene (TSG) and somatic mutation of SPOP was detected in prostate cancer (PCA). The aim of this study was to see whether alterations of SPOP protein expression and somatic mutation of SPOP gene are features of cancers. In this study, we analyzed SPOP somatic mutation in 45 gastric (GC), 45 colorectal cancer (CRC) and 45 PCA by single-strand conformation polymorphism (SSCP). Also, we analyzed SPOP protein expression in 60 GC, 60 CRC and 60 PCA by immunohistochemistry. Overall, we detected three somatic missense mutations of SPOP gene in the coding sequences (p.Ser14Leu, p.Tyr87Cys and p.Phe133Leu). The mutations were observed in two PCA and one CRC. Of note, the p.Phe133Leu was a recurrent mutation reported in an earlier study. In the immunohistochemistry, SPOP protein was expressed in normal gastric, colonic and prostate epithelial cells, whereas it was lost in 30% of GC, 20% of CRC and 37% of PCA. Our data indicate that loss of SPOP expression was common in GC, CRC and PCA, but somatic mutation of SPOP in this study was rare in these tumors. Also, the data provide a possibility that loss of expression of SPOP gene might play a role in cancer pathogenesis by altering TSG functions of SPOP.