As a member of the hox gene family, hoxB4 gene encodes a class of DNA-dependent homeobox domain nucleoprotein, which is a specific transcription factor, playing an important role in regulating the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs). Therefore, it is important to understand the mechanisms involved in regulating expression of hoxB4 in the HSC. Previous studies have suggested that some hoxB4 upstream regulatory factors, such as USF-1 (upstream activating factor -1), USF-2 (upstream activating factor -2) and NF-Y complex, as well as hematopoietic cytokines, such as platelet growth factor (TPO) and Wnt3a protein, play important regulatory roles in the expression of hoxB4 in hematopoietic stem cells. In this review the structure and biological characteristics of hoxB4, mechanisms involved in regulating expression of hoxB4 in the HSC are summarized.
CCAAT-Binding Factor ; metabolism ; Gene Expression Regulation ; Genes, Homeobox ; genetics ; physiology ; Hematopoietic Stem Cells ; metabolism ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; Humans ; Transcription Factors ; genetics ; metabolism ; physiology ; Upstream Stimulatory Factors ; metabolism ; Wnt Proteins ; metabolism ; Wnt3 Protein ; Wnt3A Protein

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.
Humans ; Phenotype ; Wnt Proteins

Wnt3a, one of Wnt family members, plays key roles in regulating pleiotropic cellular functions, including self-renewal, proliferation, differentiation, and motility. Accumulating evidence has suggested that Wnt3a promotes or suppresses tumor progression via the canonical Wnt signaling pathway depending on cancer type. In addition, the roles of Wnt3a signaling can be inhibited by multiple proteins or chemicals. Herein, we summarize the latest findings on Wnt3a as an important therapeutic target in cancer.
Cell Division ; physiology ; Gene Expression Regulation, Neoplastic ; physiology ; Humans ; Neoplasm Proteins ; metabolism ; physiology ; Neoplasms ; genetics ; metabolism ; pathology ; Tumor Cells, Cultured ; Wnt Signaling Pathway ; physiology ; Wnt3A Protein ; metabolism ; physiology

Humans ; Proto-Oncogene Proteins ; metabolism ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; Wnt-5a Protein

BACKGROUND: Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway. METHODS: Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting. RESULTS: IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells. CONCLUSION HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.
Cell Line, Tumor ; Cells, Cultured ; Chondrocytes/metabolism* ; Glycogen Synthase Kinase 3 beta/genetics* ; Histone Deacetylases/genetics* ; Humans ; Interleukin-1beta/pharmacology* ; Matrix Metalloproteinase 13/metabolism* ; Matrix Metalloproteinase 3 ; Repressor Proteins ; Wnt Signaling Pathway ; Wnt3A Protein/genetics* ; beta Catenin/metabolism*

OBJECTIVEPrevious studies suggest that hyperbaric oxygen (HBO) treatment promotes the proliferation of neurocytes in neonatal rats following hypoxic-ischemic brain damage (HIBD). The Wnt signaling pathway is associated with neurogenesis. This study examined whether HBO promoted neural stem cells (NSCs) proliferation after HIBD, and whether that the proliferation correlated with Wnt-3 protein expression.

METHODSSeven-day-old Sprague-Dawley rats were randomly divided into three groups: normal control, hypoxia-ischemia (HI), and HI-HBO. HI was induced by the ligation of left common carotid artery, followed by a 2-hr exposure to 8% O2 in the latter two groups. HBO was administered 3 hrs after HI in the HI-HBO group for continuous 7 days (2 atmospheres absolute, once daily). The proliferating NSCs in the subventricular zone (SVZ) was examined by BrdU/nestin immunofluorescence and the expression of Wnt-3 protein in NSCs was examined by nestin/Wnt-3 immunofluorescence at 6 and 24 hrs and at 3, 7 and 14 days of HI. The cellular expressions of nestin and Wnt-3 protein were analyzed by laser scanning confocal microscopy. The linear regression analysis was used to evaluate the correlation between cellular Wnt-3 and nestin protein. The expressions of nestin and Wnt-3 protein in the ischemic cerebral hemisphere were analyzed with Western blotting.

RESULTSThe number of BrdU/nestin positive cells in the SVZ increased 3 hrs after HBO therapy, peaked at 7 days and remained at a higher level until 14 days after HBO therapy in the HI-HBO group compared with the normal control and the HIBD groups. The level of Wnt-3 protein in NSCs increased significantly 3 hrs after HBO therapy, peaked at 3 days and remained at high levels until 14 days after HBO therapy in the HI-HBO group compared with the normal control and the HIBD groups. The level of cellular nestin protein was closely correlated with the level of cellular Wnt-3 protein (r = 0.893, P < 0.05). The Western blotting analysis demonstrated increased Wnt-3 and nestin protein expressions in the ischemic cerebral hemispheres.

CONCLUSIONSHBO treatment promotes the proliferation of NSCs in HIBD neonatal rats, which is correlated with the activation of Wnt signaling.

Animals ; Animals, Newborn ; Blotting, Western ; Bromodeoxyuridine ; metabolism ; Cell Proliferation ; Female ; Fluorescent Antibody Technique ; Hyperbaric Oxygenation ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; therapy ; Intermediate Filament Proteins ; Male ; Nerve Tissue Proteins ; Nestin ; Neurons ; cytology ; Rats ; Stem Cells ; cytology ; Wnt Proteins ; analysis ; Wnt3 Protein

Wnt/β-catenin signaling pathway has a close relationship with cancer and is abnormally activated in many human cancers. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, but the molecular mechanisms of HCC are still poorly understood. Current studies indicate that Wnt/β-catenin signaling pathway plays a key role in the development and progression of HCC. Validating the role and mechanism of Wnt/β-catenin signaling pathway in HCC will provide a theoretical basis for early diagnosis and treatment of HCC. In this review, we summarize the role of Wnt/β-catenin signaling pathway in HCC and the progress of current researches.
Carcinogenesis ; Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms ; Wnt Proteins ; Wnt Signaling Pathway ; beta Catenin

Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway

Tooth agenesis is the most common form of congenital craniofacial dysplasia seen in stomatology clinics, which may be caused by genetic and/or environmental factors. Tooth development is regulated by a series of signaling pathways, and variants in any of these strictly balanced signaling cascades can result in tooth agenesis and/or other oral defects. Notably, variants of genes of the Wnt/beta-catenin signaling pathway are important cause for both non-syndromic and syndromic tooth agenesis. This article has provided a review for the molecular genetics of tooth agenesis associated with Wnt/beta-catenin signaling pathway, which may shed lights on the etiology and molecular mechanism of this disease.
Anodontia/genetics* ; Genetic Research ; Humans ; Tooth ; Wnt Proteins/genetics* ; Wnt Signaling Pathway/genetics*

A number of studies have demonstrated that the methylation of Dickkopf-1 (DKK1) gene promoter is related with the occurrence and development of many neoplastic diseases. By means of binding with corresponding receptors, DKK1 blocks the transduction pathway of Wnt/β-catenin/TCF and inhibits the proliferation and invasion of tumor cells, inducing apoptosis. Leukemia is a hyperplastic disease of hematopoietic stem cell malignant clone. Its pathogenesis has been confirmed to be closely related with the aberrant activation of Wnt signaling pathway. This pathway is associated with the self-renewal and proliferation of the hematopoietic stem cells, which can regulate growth, differentiation, migration of the cells, angiogenesis and embryonic development. Its expression is regulated by some suppressor genes like Dickkopf 1 (DKK1). Leukemia often accompanied by methylation modification of the DKK1 gene, so as to leads to silencing itself and activation of the Wnt signaling pathway, which cause the occurrence of leukemia. Some therapeutic methods on leukemia aiming at DKK1 gene have been reported, among which DKK1 gene was demethylated. The intensive study on the expression and function of DKK1 should be important for the early diagnosis, treatment and prognosis. This article reviews the current progress in this field.
Apoptosis ; Cell Differentiation ; Gene Expression Regulation, Leukemic ; Humans ; Intercellular Signaling Peptides and Proteins ; Leukemia ; Wnt Proteins ; Wnt Signaling Pathway ; beta Catenin