A novel gene ZNF862 causes hereditary gingival fibromatosis

Wu, Juan; Chen, Dongna; Huang, Hui; Luo, Ning; Chen, Huishuang; Zhao, Junjie; Wang, Yanyan; Zhao, Tian; Huang, Siyuan; Ren, Yang; Zhai, Teng; Sun, Weibin; Li, Houxuan; Li, Wei

doi:10.7554/elife.66646

Cited by 7 publications

(11 citation statements)

References 34 publications

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“…18 Although ZNF862 function is not clearly known, the functional study reported by the authors supports the biological role of ZNF862 in increasing the synthesis of profibrotic factors, particularly COL1A1 (collagen type I alpha 1 chain). 18 The aim of the present study was to apply WES to identify the genetic mutations associated with members of four families with clinical diagnosis of HGF. The genetic analysis led to identification of two new variants in known HGF genes (REST and SOS1) and two mutations in new HGF genes, including ALK (ALK receptor tyrosine kinase) and CD36 (collagen type I receptor and thrombospondin receptor).…”

Section: Introductionmentioning

confidence: 70%

“…characterized two novel REST mutations (c.2449C > T, p.R817* and c.2771_2793dup, p.E932Kfs*3) in Chinese families with HGF. More recently, a missense mutation in the zinc finger protein 862 gene ( ZNF862 ), located on chromosome 7q36.1, was reported in 13 individuals with autosomal‐dominant HGF in a four‐generation Chinese family 18 . Although ZNF862 function is not clearly known, the functional study reported by the authors supports the biological role of ZNF862 in increasing the synthesis of profibrotic factors, particularly COL1A1 (collagen type I alpha 1 chain) 18 …”

Section: Introductionmentioning

confidence: 96%

“…More recently, a missense mutation in the zinc finger protein 862 gene ( ZNF862 ), located on chromosome 7q36.1, was reported in 13 individuals with autosomal‐dominant HGF in a four‐generation Chinese family 18 . Although ZNF862 function is not clearly known, the functional study reported by the authors supports the biological role of ZNF862 in increasing the synthesis of profibrotic factors, particularly COL1A1 (collagen type I alpha 1 chain) 18 …”

Section: Introductionmentioning

confidence: 96%

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New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes

Machado

Andrade

Pêgo

et al. 2022

Journal of Periodontology

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Background Hereditary gingival fibromatosis (HGF) is an uncommon genetic condition characterized by slow but progressive fibrous, non‐hemorrhagic, and painless growth of the gingival tissues due to the increased deposition of collagen and other macromolecules of the extracellular matrix. HGF occurs in approximately 1:750,000 individuals and can exhibit dominant or recessive inheritance. To date, five loci (2p21‐p22, 2p22.3‐p23.3, 4q12, 5q13‐q22, and 11p15) and three genes [REST (RE1‐silencing transcription factor), SOS1 (Son‐of‐Sevenless‐1), and ZNF862 (zinc finger protein 862 gene)] have been associated with HGF. Here, our study aimed to identify genetic variants associated with HGF by applying whole‐exome sequencing (WES) and bioinformatics analyses. Methods Thirteen Brazilian individuals with HGF and nine relatives without HGF from four unrelated families were chosen for our investigation. Blood collected from the patients and their relatives were used for WES. Five Web‐available tools, namely, CADD, PolyPhen, SIFT, Mutation Taster, and Franklin's algorithms, were used to predict protein damage. Results WES revealed pathogenic variants affecting the known HGF genes REST (c.1491_1492delAG) and SOS1 (c.3265_3266insTAAC) in two families. Additionally, potentially pathogenic variants segregating in the other two families were mapped to ALK receptor tyrosine kinase gene (ALK) (c.361C > T) and to collagen type I receptor and thrombospondin receptor gene (CD36) (c.1133G > T). Conclusion Our findings reinforce the high genetic heterogeneity of HGF, identifying new variants in HGF known genes (REST and SOS1) and ALK and CD36 as new genes that cause HGF.

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Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

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New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes

Machado

Andrade

Pêgo

et al. 2022

Journal of Periodontology

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“…Besides, the son of sevenless-1 gene (SOS1, GINGF1) [42] and the RE1-silencing transcription factor gene (REST, GINGF5)[46, 47] were clearly associated with the occurrence of HGF [48,49]. Moreover, ALK, CD36, and ZNF862 (zinc nger protein 862) are new genes found recently, which are also associated with HGF [50,51]. Histologically, HGF is characterized by proliferative brous overgrowth of the gingival tissues and causes enlargement of the attached gingival tissue [7].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based approach to construct a ceRNA network between periodontitis and hereditary gingival fibroplasia

et al. 2023

Preprint

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Background Hereditary gingival fibromatosis (HGF) is a rare, hereditary oral disease that would cover the crown of teeth, resulting in tooth migration, abnormal occlusion, or psychological issues, mostly seen in children and adolescents. Periodontitis is a chronic inflammatory illness that may lead to bone and tooth loss. While HGF patients with periodontitis often have severe clinical outcomes, its pathogenesis is not fully understood. This study was to construct a competing endogenous RNA (ceRNA) network between HGF and periodontitis using a bioinformatics approach, in order to explore the pathogenesis of these two co-existence diseases.Methods Differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus (GEO) database between HGF and periodontitis. The Search Tool for Interacting Genes (STRING) database was used to retrieve functional intersection parts between overlapping DEGs for constructing the protein-protein interaction (PPI) network analysis. To build a ceRNA network, 6 databases were used to predict the microRNAs(miRNAs) for the above-mentioned top 5 key genes by using R software, and StarBase (v2.0) database was then predicted to acquire the long non-coding RNAs (lncRNAs) that interact with the aforementioned differentially expressed miRNAs.Results 40 intersecting genes were identified through differential expression analysis and the top 5 key targets, including IL6, FLG2, LOR, KRT2, and LCE2B, were recognized as core targets between HGF and periodontitis from the PPI network. A ceRNA network was constructed with 3 mRNAs (IL6, FLG2, and KRT2), 3 miRNAs (hsa-miR-149-5p, hsa-miR-760, and hsa-miR-376c-3p), and 4 lncRNAs (KCNQ1OT1, NEAT1, HELLPAR, LRRC75A-AS1).Conclusion Current results are obtained by bioinformatics approaches, although its accuracy still needs verification by follow-up biological experiments, this novel ceRNA network may help us to reveal the correlation between HGF and periodontitis deeply, provide diagnosis molecular markers, and develop new therapeutic options for patients with HGF and periodontitis in near future.

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“…7 In our previous study, we found the mutation of ZNF862 (c.2812G > A) was associated with a Chinese family. 8 However, the biological function of the ZNF862 was unknown and the related experiment evidence was absent.…”

Section: Introductionmentioning

confidence: 99%

ZNF862 induces cytostasis and apoptosis via the p21‐RB1 and Bcl‐xL‐Caspase 3 signaling pathways in human gingival fibroblasts

Zhu,

Zhao,

et al. 2024

J of Periodontal Research

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ObjectiveThis study investigates the effects of ZNF862 on the proliferation and apoptosis of human gingival fibroblasts and their related mechanisms.BackgroundAs a major transcription factor family, zinc finger proteins (ZFPs) regulate cell differentiation, growth, and apoptosis through their conserved zinc finger motifs, which allow high flexibility and specificity in gene regulation. In our previous study, ZNF862 mutation was associated with hereditary gingival fibromatosis. Nevertheless, little is known about the biological function of ZNF862. Therefore, this study was aimed to reveal intracellular localization of ZNF862, the influence of ZNF862 on the growth and apoptosis of human gingival fibroblasts (HGFs) and its potential related mechanisms.MethodsImmunohistochemistry, immunofluorescence staining, and western blotting were performed to determine the intracellular localization of ZNF862 in HGFs. HGFs were divided into three groups: ZNF862 overexpression group, ZNF862 interference group, and the empty vector control group. Then, the effects of ZNF862 on cell proliferation, migration, cell cycle, and apoptosis were evaluated. qRT‐PCR and western blotting were performed to further explore the mechanism related to the proliferation and apoptosis of HGFs.ResultsZNF862 was found to be localized in the cytoplasm of HGFs. In vitro experiments revealed that ZNF862 overexpression inhibited HGFs proliferation and migration, induced cell cycle arrest at the G0/G1‐phase and apoptosis. Whereas, ZNF862 knockdown promoted HGFs proliferation and migration, accelerated the transition from the G0/G1 phase into the S and G2/M phase and inhibited cell apoptosis. Mechanistically, the effects of ZNF862 on HGFs proliferation and apoptosis were noted to be dependent on inhibiting the cyclin‐dependent kinase inhibitor 1A (p21)‐retinoblastoma 1 (RB1) signaling pathway and enhancing the B‐cell lymphoma‐extra‐large (Bcl‐xL)‐Caspase 3 signaling pathway.ConclusionOur results for the first time reveal that ZNF862 is localized in the cytoplasm of HGFs. ZNF862 can inhibit the proliferation of HGFs by inhibiting the p21‐RB1 signaling pathway, and it also promotes the apoptosis of HGFs by enhancing the Bcl‐xL‐Caspase 3 signaling pathway.

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A novel gene ZNF862 causes hereditary gingival fibromatosis

Cited by 7 publications

References 34 publications

New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes

New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes

Bioinformatics-based approach to construct a ceRNA network between periodontitis and hereditary gingival fibroplasia

ZNF862 induces cytostasis and apoptosis via the p21‐RB1 and Bcl‐xL‐Caspase 3 signaling pathways in human gingival fibroblasts

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