Project description:Talin-1, a macromolecular cytoskeletal protein, promotes hepatocellular carcinoma (HCC) progression. However the underlying mechanism of Talin-1 in HCC remains unclear. Analysis of the gene expression profiles of normal control HCC cell (MHCC-97L) and knockdown Talin-1 HCC cells (sh-Talin-1 MHCC-97L).
Project description:Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma.
Project description:Hepatocellular carcinoma (HCC) is one of the most malignant and lethal cancers in the world. Its complex process of molecular pathogenesis indicates that HCC is caused by multiple etiological factors and involves multiple types of genes during its development and progression. In the current study, we performed a microarray analysis on the mRNA transcriptome of HCC (C), peri-cancerous liver (P) and normal liver (N) tissues. After integrating these results with information from the Gene Ontology and KEGG Pathway databases, we analyzed the potential interactions between different genes and constructed an interaction network, and identified the regulator, mediator and effector genes in this interaction network. Three types of tissues: 49 pairs of homogenous human primary hepatocellular carcinoma (Cancer, C) and pericancer liver tissues (Pericancer, P), 10 normal liver tissues (Normal, N). Three-condition experiment, HCC vs. Normal and Pericancer vs. Normal.
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.