RESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.
Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas S100/metabolismo , Adenocarcinoma/mortalidade , Anexina A2/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Fatores Quimiotáticos/metabolismo , Bases de Dados Genéticas , Progressão da Doença , Humanos , Pâncreas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , RNA Mensageiro/metabolismo , Proteína A6 Ligante de Cálcio S100/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Proteínas S100/genética , Transcrição GênicaRESUMO
Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-ß1/Smad and ß -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/patologia , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Transdução de Sinais , Animais , Ciclo Celular , Proliferação de Células , Progressão da Doença , Humanos , Mitose , Neoplasias/genética , Neoplasias/metabolismoRESUMO
The sex of relatively primitive animals such as invertebrates is mostly determined by environmental factors and chromosome ploidy. Heteromorphic chromosomes may also play an important role, as in the ZW system in lepidopterans. However, the mechanisms of these various sex determination systems are still largely undefined. In the present study, a Masculinizer gene (Ar-Masc) was identified in the crustacean Artemia franciscana Kellogg 1906. Sequence analysis revealed that the 1140-bp full-length open reading frame of Ar-Masc encodes a 380-aa protein containing two CCCH-type zinc finger domains having a high degree of shared identities with the MASC protein characterized in the silkworm Bombyx mori, which has been determined to participate in the production of male-specific splice variants. Furthermore, although Ar-Masc could be detected in almost all stages in both sexual and parthenogenetic Artemia, there were significant variations in expression between these two reproductive modes. Firstly, qRT-PCR and Western blot analysis showed that levels of both Ar-Masc mRNA and protein in sexual nauplii were much higher than in parthenogenetic nauplii throughout the hatching process. Secondly, both sexual and parthenogenetic Artemia had decreased levels of Ar-Masc along with the embryonic developmental stages, while the sexual ones had a relatively higher and more stable expression than those of parthenogenetic ones. Thirdly, immunofluorescence analysis determined that sexual individuals had higher levels of Ar-MASC protein than parthenogenetic individuals during embryonic development. Lastly, RNA interference with dsRNA showed that gene silencing of Ar-Masc in sexual A. franciscana caused the female-male ratio of progeny to be 2.19:1. These data suggest that Ar-Masc participates in the process of sex determination in A. franciscana, and provide insight into the evolution of sex determination in sexual organisms.
Assuntos
Artemia/genética , Proteínas de Artrópodes/genética , Processos de Determinação Sexual/genética , Diferenciação Sexual/genética , Sequência de Aminoácidos , Animais , Artemia/embriologia , Artemia/metabolismo , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Western Blotting , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Larva/genética , Masculino , Partenogênese/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Fatores de TempoRESUMO
In arthropods, mature females under certain conditions produce and release encysted gastrula embryos that enter diapause, a state of obligate dormancy. The process is presumably regulated by diapause hormone (DH) and diapause hormone receptor (DHR) that were identified in the silkworm, Bombyx mori and other insects. However, the molecular structure and function of DHR in crustaceans remains unknown. Here, a DHR-like gene from parthenogenetic Artemia (Ar-DHR) was isolated and sequenced. The cDNA sequence consists of 1410bp with a 1260-bp open reading frame encoding a protein consisting of 420 amino acid residues. The results of real-time PCR (qRT-PCR) and Western blot analysis showed that the mRNA and protein of Ar-DHR were mainly expressed at the diapause stage. Furthermore, we found that Ar-DHR was located on the cell membrane of the pre-diapause cyst but in the cytoplasm of the diapause cyst by analysis of immunofluorescence. In vivo knockdown of Ar-DHR by RNA interference (RNAi) and antiserum neutralization consistently inhibited diapause cysts formation. The results indicated that Ar-DHR plays an important role in the induction and maintenance of embryonic diapause in Artemia. Thus, our findings provide an insight into the regulation of diapause formation in Artemia and the function of Ar-DHR.
