RESUMO
Long noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism pathway. In the present research, we surveyed the expression levels and clinical significance of novel lncRNAs related to CYP24A1 and PFDN4 genes in colorectal cancer (CRC) using real-time polymerase chain reaction. Furthermore, we assessed the expression of these genes after vitamin D treatment in HCT-116 and HT-29 colon cancer cell lines. Our results indicated that the transcription of CYP24A1, PFDN4, and nearby lncRNAs was affected by vitamin D treatment in HCT-116 and HT-29 cell lines. Moreover, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 were upregulated and had the potential to distinguish colorectal cancer tissues from the adjacent tissues by the large area under the receiver operating characteristic curve (0.94, 0.66, 0.70, and 0.60, respectively). lnc-TSHZ2-19:1 expression level significantly correlated with gender (p = .03). In conclusion, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 can be used as potential diagnostic biomarkers in the specific and sensitive assessment of CRC. Besides this, vitamin D treatment may modulate the expression of these genes in a cell-specific manner.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Regulação para Cima/genética , Vitamina D3 24-Hidroxilase/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vitamina D3 24-Hidroxilase/metabolismoRESUMO
Thrombocytopenia-absent radius (TAR) syndrome is a rare genetic disorder inherited in an autosomal recessive fashion. In most patients chromosomes at 1q21.1 harbor a 200-kb deletion consisted of many genes, including RBM8A. We aimed to examine a cost-effective method for investigation a consanguineous family clinically diagnosed as TAR syndrome. A comprehensive sequencing of RBM8A identified several SNPs including two low-frequency regulatory SNPs (rs139428292 and rs201779890) in the father, the mother and the proband in which they carried A/G, G/- and A/- alleles for rs139428292, respectively. They also had G/G genotype in the father, G/- in both mother and proband for rs201779890. In addition a SNP (rs872786) was found in mother as T/- allele while father and proband have possessed A/A and A/- alleles, respectively. Further investigation determined a rare null allele in the proband using quantitative real-time PCR. We concluded that compound inheritance of a rare null allele and one of the two low-frequency noncoding SNPs (rs139428292) in RBM8A are crucial for TAR syndrome. Quantitative real-time PCR and Sanger sequencing may recruit for molecular diagnosis of TAR rather than molecular cytogenetic study.
Assuntos
Trombocitopenia/diagnóstico , Deformidades Congênitas das Extremidades Superiores/diagnóstico , Adulto , Sequência de Bases , Estudos de Casos e Controles , Síndrome Congênita de Insuficiência da Medula Óssea , Consanguinidade , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Masculino , Técnicas de Diagnóstico Molecular , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Rádio (Anatomia) , Análise de Sequência de DNA , Trombocitopenia/genética , Deformidades Congênitas das Extremidades Superiores/genética , Adulto JovemAssuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Rearranjo Gênico , Adulto , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Feminino , Proteínas Ativadoras de GTPase , Frequência do Gene , Estudos de Associação Genética , Testes Genéticos , Humanos , Reação em Cadeia da Polimerase Multiplex , Proteínas de Saccharomyces cerevisiae , Deleção de SequênciaRESUMO
BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations - four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS: Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective.
