The potential role of miR-124-3p in tumorigenesis and other related diseases.

MicroRNAs (miRNAs) are a class of single-stranded noncoding and endogenous RNA molecules with a length of 18-25 nucleotides. Previous work has shown that miR-124-3p leads to malignant progression of cancer including cell apoptosis, migration, invasion, drug resistance, and also recovers neural function, affects adipogenic differentiation, facilitates wound healing through control of various target genes. miR-124-3p has been mainly previously characterized as a tumor suppressor regulating tumorigenesis and progression in several cancers, such as hepatocellular carcinoma (HCC), gastric cancer (GC), bladder cancer, ovarian cancer (OC), and leukemia, as a tumor promotor in breast cancer (BC), and it has been also widely studied in a variety of neurological diseases, like Parkinson's disease (PD), dementia and Alzheimer's disease (AD), and cardiovascular diseases, ulcerative colitis (UC), acute respiratory distress syndrome (ARDS).

CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v-crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK-like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown.

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.

Background: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear.

Crystal structure of tetra-aqua-bis-(pyrimidin-1-ium-4,6-diolato-κ)manganese(II).

The Mn ion in the structure of the mononuclear title compound, [Mn(CHNO)(HO)], is situated on an inversion center and is coordinated by two O atoms from two deprotonated 4,6-di-hydroxy-pyrimidine ligands and by four O atoms from water mol-ecules giving rise to a slightly distorted octa-hedral coordination sphere. The complex includes an intra-molecular hydrogen bond between an aqua ligand and the non-protonated N ring atom. The extended structure is stabilized by inter-molecular hydrogen bonds between aqua ligands, by hydrogen bonds between N and O atoms of the ligands of adjacent mol-ecules, and by hydrogen bonds between aqua ligands and the non-coordinating O atom of an adjacent mol-ecule.

Comparing hydrazine-derived reactive groups as inhibitors of quinone-dependent amine oxidases.

Lysyl oxidase has emerged as an important enzyme in cancer metastasis. Its activity has been reported to become upregulated in several types of cancer, and blocking its activity has been shown to limit the metastatic potential of various cancers. The small-molecules phenylhydrazine and β-aminopropionitrile are known to inhibit lysyl oxidase; however, issues of stability, toxicity, and poorly defined mechanisms limit their potential use in medical applications.

Role of annexin A6 in cancer.

Annexin A6 (AnxA6) is a member of a conserved superfamily of Ca-dependent membrane-binding annexin proteins. It participates in membrane and cytoskeleton organization, cholesterol homeostasis, membrane trafficking, cell adhesion and signal transduction. The expression levels of AnxA6 are closely associated with melanoma, cervical cancer, epithelial carcinoma, breast cancer, gastric cancer, prostate cancer, acute lymphoblastic leukemia, chronic myeloid leukemia, large-cell lymphoma and myeloma.

Comparative binding affinities of flavonoid phytochemicals with bovine serum albumin.

Dietary flavonoids show beneficial effects in the prevention of chronic diseases. However, flavonoid bioavailability is poor, probably due to their interaction with serum albumins. In the current work, the binding interactions of eight related flavonoids, sharing a similar core structure, with bovine serum albumin (BSA) were investigated by fluorescence spectroscopy.

Annexin A11 in disease.

Ubiquitously expressed in many cell types, annexin A11 (Anxa11) is a member of the multigene family of Ca(2+)-regulated phospholipid-dependent and membrane-binding annexin proteins. Studies have shown that Anxa11 plays an important role in cell division, Ca(2+) signaling, vesicle trafficking and apoptosis. The deregulation and mutation of Anxa11 are involved in systemic autoimmune diseases, sarcoidosis and the development, chemoresistance and recurrence of cancers.

Potential role of annexin A7 in cancers.

Annexin A7 (Anxa7) is a member of the multigene annexin superfamily of Ca(2+)-regulated and phospholipid-binding proteins. Accumulated evidence indicates that the deregulation, loss of heterozygosity (LOH) and subcellular localization of Anxa7 are associated with the occurrence, invasion, metastasis and progression of a variety of cancers. Anxa7 appears to have a tumor-suppression role in glioblastoma, glioblastoma multiforme (GBM), melanoma and prostate cancer (CaP) but, controversially and interestingly, Anxa7 also appears to promote the development and malignancies of liver cancer, gastric cancer (GC), nasopharyngeal carcinoma (NPC), colorectal cancer (CRC) and breast cancer (BC).

ACTB in cancer.

Beta-actin (ACTB) has traditionally been regarded as an endogenous housekeeping gene and has been widely used as a reference gene/protein in quantifying expression levels in tumors. However, ACTB is closely associated with a variety of cancers and accumulating evidence indicates that ACTB is de-regulated in liver, melanoma, renal, colorectal, gastric, pancreatic, esophageal, lung, breast, prostate, ovarian cancers, leukemia and lymphoma. ACTB is generally found to be up-regulated in the majority of tumor cells and tissues.

Identification of the copper-binding ligands of lysyl oxidase.

In order to identify the ligands coordinating with copper in lysyl oxidase, the enzyme was expressed in an E. coli expression system and active enzyme obtained after refolding in the presence of Cu(II). The five histidines found in the putative copper-binding region were sequentially mutated to alanines and the enzymatic activities of the resultant mutants were monitored, together with the copper content, the CD and fluorescence spectra, and the redox-cycling activity.

Identification of the disulfide bonds of lysyl oxidase.

Proteolytic digestion of bovine aortic lysyl oxidase followed by tandem mass spectrometry has enabled assignment of all five disulfide bonds. The results indicate that the enzyme has a very stable central core containing three disulfide bonds, the lysyl tyrosyl quinone cross-link and the copper. This core is well isolated from solvent with the result that the oxidized (normal) form of the enzyme is remarkably resistant to proteolysis and is unusually stable at high temperatures and in the presence of denaturants.

Purification of high yields of catalytically active lysyl oxidase directly from Escherichia coli cell culture.

Lysyl oxidase is a highly insoluble enzyme requiring high concentrations of urea to solubilize. A method to obtain lysyl oxidase in high yields directly from an Escherichia coli culture without the need for refolding of inclusion bodies has been developed using nutrient rich media. pET21b was used to overexpress the lysyl oxidase enzyme and to introduce a C-terminal 6X histidine tag for purification.

Modeling Cu(II) binding to peptides using the extensible systematic force field.

The utility of the extensible systematic force field (ESFF) was tested for copper(II) binding to a 34-amino-acid Cu(II) peptide, which includes five histidine residues and is the putative copper-binding site of lysyl oxidase. To improve computational efficiency, distance geometry calculations were used to constrain all combinations of three histidine ligands to be within bonding distance of the copper and the best results were utilized as starting structures for the ESFF computations. All likely copper geometries were modeled, but the results showed only a small dependence on the geometrical model in that all resulted in a distorted square pyramidal geometry about the copper, some of the imidazole rings were poorly oriented for ligation to the Cu(II), and the copper-nitrogen bond distances were too long.

A C-terminal hydrophobic, solvent-protected core and a flexible N-terminus are potentially required for human papillomavirus 18 E7 protein functionality.

The oncogenic potential of the high-risk human papillomavirus (HPV) relies on the expression of genes specifying the E7 and E6 proteins. To investigate further the variation in oligomeric structure that has been reported for different E7 proteins, an HPV-18 E7 cloned from a Hispanic woman with cervical intraepithelial neoplasia was purified to homogeneity most probably as a stable monomeric protein in aqueous solution. We determined that one zinc ion is present per HPV-18 E7 monomer by amino acid and inductively coupled plasma-atomic emission spectroscopy analysis.

Biochemical, functional and structural characterization of Akbu-LAAO: a novel snake venom L-amino acid oxidase from Agkistrodon blomhoffii ussurensis.

An L-amino acid oxidase (Akbu-LAAO) was isolated from the venom of Agkistrodon blomhoffii ussurensis snake using DEAE Sephadex A-50 ion-exchange, Sephadex G-75 gel filtration, and high performance liquid chromatographies. The homogeneity and molecular mass of Akbu-LAAO were analyzed by SDS-PAGE and MALDI-TOF spectrometry. The sequences of ten peptides from Akbu-LAAO were established by HPLC-nESI-MS/MS analysis.

Proteomics analysis of two mice hepatocarcinoma ascites syngeneic cell lines with high and low lymph node metastasis rates provide potential protein markers for tumor malignancy attributes to lymphatic metastasis.

Lymph node metastasis (LNM) is recognized as an important factor involved in the tumor malignancy progression. Our previous study has indicated that the hepatocarcinoma cell line with 75% of LNM (Hca-F)-cell-induced neoplasia and the hepatocarcinoma cell line with 25% of LNM-induced neoplasia are accompanied with high (75%) and low (25%) incidences of LNM. In the current study, 62 and 54 protein spots were observed up-regulated and down-regulated in Hca-F cell relative to the hepatocarcinoma cell line with 25% of LNM by 2-D DIGE.

A novel phospholipase A2 from Agkistrodon blomhoffii ussurensis venom: purification, proteomic, functional and structural characterizations.

A phospholipase A(2) was isolated from the snake venom of Chinese Agkistrodon blomhoffii Ussurensis by column chromatography using DEAE Sephadex A-50 ion-exchange chromatography, Sephadex G-75 gel filtration chromatography and Mono Q ion-exchange chromatography, and designated as Akbu-PLA(2). It showed an average molecular mass of 13,980+/-3 amu determined by MALDI TOF mass spectrometry. Protein identification results from HPLC-nESI-MS/MS analysis indicated that the Akbu-PLA(2) was a new snake venom acidic PLA(2).

A novel serine protease from the snake venom of Agkistrodon blomhoffii ussurensis.

A novel serine protease, ABUSV-SPase, was isolated to homogeneity for the first time from Chinese Agkistrodon blomhoffii ussurensis snake venom, and its enzymatic and structural properties were characterized by multiple techniques. ABUSV-SPase is a stable monomeric protein with a molecular mass of 26,752.6a.

High-performance liquid chromatography/nano-electrospray ionization tandem mass spectrometry, two-dimensional difference in-gel electrophoresis and gene microarray identification of lymphatic metastasis-associated biomarkers.

The potential biomarkers for the lymphatic metastatic process of mouse hepatocarcinoma were investigated by using two-dimensional difference in-gel electrophoresis (2D DIGE), high-performance liquid chromatography/nano-electrospray ionization tandem mass spectrometry (HPLC/nESI-MS/MS) and GeneChip. 2D DIGE was performed to screen and quantify the differentially expressed proteins between two well-established mouse hepatocarcinoma cell lines, Hca-F with 75% and Hca-P with 25% metastasis rate of lymph node potentials. The protein spots in the gel were visualized by the highly sensitive Deep Purple (GE Healthcare) fluorescent stain.

A novel plasminogen activator from Agkistrodon blomhoffii Ussurensis venom (ABUSV-PA): purification and characterization.

A plasminogen activator with arginine ester hydrolysis activity (ABUSV-PA) has been identified and purified to homogeneity from Chinese Agkistrodon blomhoffii Ussurensis snake venom. ABUSV-PA, a monomeric protein with molecular mass of 27815.2 Da, was purified 180-fold with 0.

Characterization of a fibrinolytic enzyme (ussurenase) from Agkistrodon blomhoffii ussurensis snake venom: insights into the effects of Ca2+ on function and structure.

Fibrino(geno)lytic enzymes from snake venoms have been identified as high quality therapeutic agents for treatment of blood clots and strokes. They act on fibrinogen and fibrin, leading to defibrinogenation of blood, lysis of fibrin, and a consequent decrease in blood viscosity. In this work, a fibrinolytic enzyme (ussurenase) from China Agkistrodon blomhoffii Ussurensis snake venom, was purified to homogeneity, identified as a stable 23,367.