ABSTRACT
BACKGROUND: The role of ERBB4 in liver disease has seldom been reported. This study aims to find genetic markers at ERBB4 for chronic hepatitis B virus (HBV) infection and determine the role of ERBB4 in liver injury. METHODS: We selected and genotyped three single nucleotide polymorphisms and one insertion/deletion (Ins/Del) at the 5' and 3' untranslated region (UTR) of ERBB4 in a case-control study including 1344 pairs of HBV carriers and HBV natural clearance subjects. The luciferase reporter system was applied to study the regulative role of Ins/Del on ERBB4. Further, ERBB4 knockout mice were used to study the role of ERBB4 in liver injury. Proteomic quantification was performed by HPLC-MS/MS analysis to identify liver protein profile change between liver-specific ERBB4 knockout and control mice. RESULTS: rs6147150 Ins/Del and rs1836724 T>C at the 3' UTR of ERBB4 were associated with reduced risk of chronic HBV infection (P = 0.002 and 0.004, respectively). Besides, the 12bp deletion at the 3' UTR increased ERBB4 expression due to lacking let-7c binding site. In addition, loss of ERBB4 led to more severe acute or chronic inflammation in mouse liver injury models. Further, quantitative proteomic analysis and data from the cancer genome atlas revealed that ACLY, an enzyme key for de novo lipogenesis, was negatively correlated with ERBB4. CONCLUSIONS: ERBB4 plays protective role from liver injury and its 3'UTR genetic variants could be genetic markers for chronic HBV infection.
Subject(s)
Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/virology , Liver Diseases/complications , Polymorphism, Single Nucleotide/genetics , Receptor, ErbB-4/genetics , Animals , Case-Control Studies , Disease Models, Animal , Follow-Up Studies , HeLa Cells , Hep G2 Cells , Humans , Inflammation/etiology , Inflammation/pathology , Liver Diseases/genetics , Liver Diseases/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Prognosis , Proteomics/methods , Receptor, ErbB-4/metabolism , Tandem Mass SpectrometryABSTRACT
The epidermal growth factor receptor (EGFR) is implicated in many types of cancer, including colorectal cancer (CRC), and has become one of the most common candidates for targeted therapy. Here, we found that Erbin, a member of the leucine-rich repeat and PDZ domain (LAP) family, plays a key role in EGFR signalling. Erbin inhibited EGFR ubiquitination and stabilized the EGFR protein by interacting with c-Cbl. Moreover, the PDZ domain of Erbin was critical for the interaction between Erbin and c-Cbl and EGFR ubiquitination. Interestingly, Erbin expression was elevated in tumour samples from CRC patients, increased in advanced clinical stage disease and correlated with EGFR expression. In vivo studies using mouse xenograft models of CRC showed that Erbin promotes tumour growth, and that the effects of Erbin on tumour growth are mainly related to the regulatory effects of Erbin on EGFR. The azoxymethane (AOM)-induced colon carcinogenesis model in Erbin(ΔC) (/) (ΔC) mice, with the PDZ domain of Erbin deleted, demonstrated that the PDZ domain of Erbin and its regulation of EGFR signalling are necessary for the tumourigenesis and tumour growth of CRC. We found that Erbin promotes tumourigenesis and tumour growth in CRC by stabilizing EGFR. Our study sheds light on developing Erbin, especially its PDZ domain, as a potential target for CRC treatment.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carrier Proteins/metabolism , Cell Transformation, Neoplastic/metabolism , Colorectal Neoplasms/metabolism , ErbB Receptors/metabolism , Proto-Oncogene Proteins c-cbl/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Carrier Proteins/genetics , Cell Transformation, Neoplastic/genetics , Colorectal Neoplasms/genetics , Disease Progression , Down-Regulation , Humans , Intracellular Signaling Peptides and Proteins , Mice , Signal Transduction/genetics , Signal Transduction/physiology , UbiquitinationABSTRACT
Iron, as one of the essential mineral elements for algae growth, plays an extremely important role in the physiological processes such as plant photosynthesis, respiration, nitrogen fixation, protein and nucleic acid synthesis. In view of the fact that iron in different forms could be absorbed and utilized by algae, the existing forms and circulation approaches in the aquatic environment, the absorption mechanism by algae, and the effects on algae growth and microcystin synthesis were reviewed in this paper. The relevant microcystin synthesis genes and their expression under iron restricted conditions were summarized, and the research directions for harmful algal blooms regulation and control by ferritin genes were suggested. It was hoped to provide the reference for eutrophication remediation technology.
Subject(s)
Harmful Algal Bloom , Iron/metabolism , Microcystins/biosynthesis , Plants/metabolism , PhotosynthesisABSTRACT
OBJECTIVE: To compare the expression of nuclear matrix proteins (NMPs) in benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 versus those in androgen-dependent human prostate cancer cell line LNCap and androgen-independent prostate cancer cell line PC-3. METHODS: We isolated NMPs from the BPH-1, LNCap and PC-3 cell lines by 2-dimensional electrophoresis (2-DE), analyzed the differentially expressed proteins by matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS), and identified them by peptide mass fingerprint and database searching. RESULTS: We successfully obtained well-resolved reproducible 2-DE patterns of NMPs in human prostate cancer cell lines, identified 12 differentially expressed NMPs including enzymes, regulatory proteins, RNA-binding protein and various other factors, 3 up-regulated and 9 down-regulated in prostate cancer cell lines. CONCLUSION: There are obvious differences in the expressions of NMPs between human prostate cancer cell lines and benign prostatic hyperplasia epithelial cell line.
Subject(s)
Nuclear Matrix-Associated Proteins/metabolism , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/metabolism , Proteome/analysis , Cell Line , Cell Line, Tumor , Electrophoresis, Gel, Two-Dimensional , Humans , Male , Proteomics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
OBJECTIVE: To introduce a novel technique of ureterointestinal anastomosis for urinary diversion and report the preliminary clinical data. METHODS: Between June 2007 and June 2011, a total of 50 patients underwent radical cystectomy and ileal neobladder for invasive bladder carcinoma or carcinoma in situ. A novel, separate and direct end-to-end technique for ureteral reimplantation to the entrance of a segment of ileum was applied. in all patients. Details are as follow. The entrance of afferent loop was divided equally in to two lumens. Then each ureter was directly, end-to-end anastomosed to the above lumens respectively after lengthwise incisions for 1.5 cm. The mean follow-up period was 22 months (range, 3 - 48 months). RESULTS: Ureterointestinal anastomosis was performed successfully in 100 units. The operative durations were (18.4 ± 4.2) minutes. Ureteral stricture developed in 4 of 100 (4%) units and refluxing in 6 of 100 (6%) units. One patient with stricture was successful repaired by balloon dilation. CONCLUSION: With low stricture and reflux rates, this novel procedure of ureterointestinal anastomosis is simple to handle and worthy of further promotion.
