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*

The balance of bone metabolism depends on the dynamic balance between bone formation and bone resorption. Wnt/β-catenin signaling pathway is involved in the regulation of bone resorption and bone formation, and plays an important role in maintaining the balance of bone metabolism. Recently, long non-coding RNA (lncRNA) is shown to play an essential role in different process of bone metabolism. LncRNA can also regulate the balance of bone metabolism via Wnt/β-catenin signaling pathway. Few studies report that lncRNA regulates bone metabolism via Wnt/β-catenin signaling pathway. Therefore, we summarize here the role of lncRNA in bone metabolism from the perspective of Wnt/β-catenin signaling pathway. LncRNA indirectly regulates Wnt/β-catenin signaling pathway by targeting miRNAs as well as activating or inhibiting Wnt/β-catenin signaling pathway via targeting the key molecules of Wnt/β-catenin signaling pathway, thus to regulate bone metabolism. These findings provide new ideas and directions for the study of the mechanism whereby lncRNA regulates bone metabolism.
Cell Line, Tumor ; Cell Proliferation ; MicroRNAs ; RNA, Long Noncoding/genetics* ; Wnt Signaling Pathway/genetics*

OBJECTIVE: In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction. METHODS: We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10^-4 using Bonferroni correction. RESULTS: A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10^-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios. CONCLUSION Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.
Asians/genetics* ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Genome-Wide Association Study ; Humans ; Wnt Signaling Pathway/genetics*

The sex-determining region Y-box 7 (Sox7) is a important member of SOX family containing high mobi- lity group (HMG), mapped to human chromosome 8p23.1. Wnt/β-catenin signaling pathway plays an important role in cell survival, differentiation, self-renewal, proliferation and apoptosis, and is closely related with carcinogenesis. SOX7 gene is likely to be a tumor suppressor gene in MDS and other hematological malignancies. As a negative regulator of the WNT/β-catenin signaling pathway, the function loss of this gene can lead to carcinogenesis. The methylation of SOX7 gene leads to the silence of this gene, resulting in tumorigenesis. The decision of hematopoietic stem cells to self-renew or differentiate is a stochastic process, but SOX7 can promote the differentiation into all blood cell types. This review focuses on the role of SOX7 in hematopoietic system development and hematological malignancies.
DNA Methylation ; Gene Silencing ; Hematologic Neoplasms ; genetics ; metabolism ; Hematopoietic System ; physiopathology ; Humans ; SOXF Transcription Factors ; genetics ; metabolism ; Wnt Signaling Pathway

Objective To study the expression and significance of leucine-rich repeat-containing G-protein coupled receptor(LGR)5/6 in childhood acute lymphoblastic leukemia(ALL). Methods A total of 39 children who had ALL and achieved complete remission on day 33 after induction therapy were enrolled.The children before induction therapy were considered as the incipient group,and those who achieved complete remission on day 33 by induction therapy were considered as the remission group.According to the degree of risk,they were assigned into 3 groups:low-risk(
Child ; Humans ; Leucine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; RNA, Messenger/genetics* ; Receptors, G-Protein-Coupled/genetics* ; Wnt Signaling Pathway

OBJECTIVETo study the effect of miR-21 down-regulation on the radiosensitivity of TE-1 cells in vitro.

METHODSTE-1 cells were transfected via lentivirus with a vector containing the antisense oligonucleotides of miR21, and the subclones with stable down-regulation of miR21 expression were selected with puromycin and designated as TE-1-miR21(-), whose expression level of miR21 was determined using real-time quantitative PCR. The radiosensitivity of TE-1 and TE-1-miR21(-) cells were evaluated with colony formation assay, and the expressions of β-catenin was determined using Western blotting and RT-PCR. Flow cytometry was used to analyze the proportion of p75NTR(+) cells in TE-1 and TE-1-miR21(-) cells.

RESULTSA cell subclone stably expressing a low level of miR21 was obtained and verified by real-time quantitative PCR. Colony formation assay showed an enhanced the radiosensitivity of TE-1-miR21(-) cells compared to parental TE-1 cells. RT-PCR revealed no significant changes in β-catenin mRNA expression in TE-1-miR21(-) cells, whereas its β-catenin protein expression was markedly suppressed by high-dose (8 and 10 Gy) irradiation. Flow cytometry assay showed a decreased proportion of p75NTR(+) cells in TE-1-miR21(-) cells compared to that in TE-1 cells.

CONCLUSIONDown-regulation of miR21 can enhance the radiosensitivity of TE-1 cells, which might result from the inactivation of wnt/β-catenin signal pathway and a decreased p75NTR(+) cell proportion.

Cell Line, Tumor ; Down-Regulation ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; MicroRNAs ; genetics ; metabolism ; Radiation Tolerance ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVE: To investigate the effects and underlying mechanism of miR-532-3p and resibufogenin (RES) by regulating Wnt/β-catenin signaling on diffuse Large B-cell lymphoma (DLBCL) cells proliferation. METHODS: DLBCL tissues and adjacent normal tissues were collected from patients had been diagnosed with DLBCL at the First Hospital of Lanzhou University from October 2019 to October 2021. Four groups including mimics-NC, miR-532-3p mimics, RES control and RES treatment in SU-DHL-4 cells were designed. The expression level of miR-532-3p was detected by RT-qPCR. The protein content of β-catenin was detected by Western blot. MTT assay was used to detect the proliferation activity of SU-DHL-4 cells. RESULTS: miR-532-3p expression was significantly decreased in DLBCL tissues compared with adjacent normal tissues (P<0.001). The miR-532-3p content in lymphoma cells was significantly lower than that in normal lymphocytes (P<0.001). After overexpression of miR-532-3p, the viability of SU-DHL 4 cells was significantly decreased (P<0.001), with a reduced expression of β-catenin (P<0.05). RES treatment inhibited the proliferation of SU-DHL-4 cells and decreased β-catenin expression in SU-DHL-4 cells compared with the control group. CONCLUSION Overexpression of miR-532-3p reduced Wnt/β-catenin signaling and inhibited the proliferation of lymphoma cells. Moreover, RES treatment inhibited lymphoma cells growth partially through Wnt/β-catenin signaling suppression.
Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; MicroRNAs/metabolism* ; Wnt Signaling Pathway ; beta Catenin

OBJECTIVETo establish a human embryonic stem cell line with stably β-catenin gene silencing by lentivirus-mediated shRNA interference.

METHODSPLKO.1-puro-β-catenin vector, a lentivirus plasmid expressing β-catenin shRNA, was packaged into 293FT cells. Human embryonic stem cells were infected with the lentivirus and the cell clones stably expressing β-catenin shRNA were selected by puromycin, with the uninfected cells and cells infected with the empty vector as the control. Real-time RT-PCR was used to evaluate the efficiency of β-catenin knocked down; β-catenin and OCT4 protein expression in the infected cells was examined using immunofluorescence assay.

RESULTSInfection with β-catenin-specific shRNA lentivirus resulted in stable interference of β-catenin expression in human embryonic stem cells, which showed a β-catenin mRNA expression of only 1% of that in the uninfected cells. Infection with the empty vector produced no obvious effect on β-catenin expression compared to the uninfected cells. In the cells infected with β-catenin shRNA lentivirus, β-catenin protein expression was almost undetectable in immunofluorescence assay, while OCT4 was still expressed after the interference.

CONCLUSIONLentiviral vector-delivered shRNA results in effective and stable β-catenin gene silencing in human embryonic stem cells.

Cell Line ; Embryonic Stem Cells ; cytology ; metabolism ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Plasmids ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection ; Wnt Signaling Pathway ; beta Catenin ; genetics ; metabolism

The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulating Wnt signaling: on one hand, Axin scaffolds the "β-catenin destruction complex" to promote β-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP5/6 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the "on" or "off" Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post-transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.
Animals ; Axin Protein ; antagonists & inhibitors ; chemistry ; metabolism ; Epigenesis, Genetic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasms ; genetics ; Protein Processing, Post-Translational ; Wnt Signaling Pathway ; genetics

OBJECTIVE: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. METHODS: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10^-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). RESULTS: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10^-4). CONCLUSION This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.
Cleft Lip/genetics* ; Cleft Palate/genetics* ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Wnt Signaling Pathway/genetics*