CCDC134 serves a crucial role in embryonic development

Yu, Biaoyi; Zhang, Tianzhuo; Xia, Peng; Gong, Xiaoting; Qiu, Xiaoyan; Huang, Jing

doi:10.3892/ijmm.2017.3196

Cited by 12 publications

(20 citation statements)

References 34 publications

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“…Recently, it has been shown that Ccdc134 is critical for mouse embryonic development . Ccdc134 −/− mice were non‐viable, with a lethality between E12.5 and E14.5, presumably related to anemia.…”

Section: Discussionmentioning

confidence: 99%

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Brunelle

Baujat

Huber

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III).

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Section: Discussionmentioning

confidence: 99%

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Brunelle

Baujat

Huber

et al. 2020

Journal of Bone and Mineral Research

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“…Two members of the γ c cytokine family effectively block CCDC134 binding to activated CD8 + T cells. This provides evidence that CCDC134 may be a potential member of the γ c cytokine family ( 31 ).…”

Section: Discussionmentioning

confidence: 82%

CCDC134 as a Prognostic-Related Biomarker in Breast Cancer Correlating With Immune Infiltrates

et al. 2022

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BackgroundThe expression of Coiled-Coil Domain Containing 134(CCDC134) is up-regulated in different pan-cancer species. However, its prognostic value and correlation with immune infiltration in breast cancer are unclear. Therefore, we evaluated the prognostic role of CCDC134 in breast cancer and its correlation with immune invasion.MethodsWe downloaded the transcription profile of CCDC134 between breast cancer and normal tissues from the Cancer Genome Atlas (TCGA). CCDC134 protein expression was assessed by the Clinical Proteomic Cancer Analysis Consortium (CPTAC) and the Human Protein Atlas. Gene set enrichment analysis (GSEA) was also used for pathway analysis. Receiver operating characteristic (ROC) curve was used to differentiate breast cancer from adjacent normal tissues. Kaplan-Meier method was used to evaluate the effect of CCDC134 on survival rate. The protein-protein interaction (PPI) network is built from STRING. Function expansion analysis is performed using the ClusterProfiler package. Through tumor Immune Estimation Resource (TIMER) and tumor Immune System Interaction database (TISIDB) to determine the relationship between CCDC134 expression level and immune infiltration. CTD database is used to predict drugs that inhibit CCDC134 and PubChem database is used to determine the molecular structure of identified drugs.ResultsThe expression of CCDC134 in breast cancer tissues was significantly higher than that of CCDC134 mRNA expression in adjacent normal tissues. ROC curve analysis showed that the AUC value of CCDC134 was 0.663. Kaplan-meier survival analysis showed that patients with high CCDC134 had a lower prognosis (57.27 months vs 36.96 months, P = 2.0E-6). Correlation analysis showed that CCDC134 mRNA expression was associated with tumor purity immune invasion. In addition, CTD database analysis identified abrine, Benzo (A) Pyrene, bisphenol A, Soman, Sunitinib, Tetrachloroethylene, Valproic Acid as seven targeted therapy drugs that may be effective treatments for seven targeted therapeutics. It may be an effective treatment for inhibiting CCDC134.ConclusionIn breast cancer, upregulated CCDC134 is significantly associated with lower survival and immune infiltrates invasion. Our study suggests that CCDC134 can serve as a biomarker of poor prognosis and a potential immunotherapy target in breast cancer. Seven drugs with significant potential to inhibit CCDC134 were identified.

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“…Our previous study showed that hemorrhages occur in the brain ventricular space and neural tube, resulting in severe overall brain disorganization and embryonic lethality from embryonic day 12.5 to birth in homozygous Ccdc134 knockout mouse embryos, but not in littermates. 14 In the present study, immunostaining using a specific anti-CCDC134 antibody was performed on sections of human cerebellar autopsy specimens and frozen cerebellar sections from wild-type mice at embryonic, adolescent and adult stages. We found that the CCDC134 protein was highly expressed in the PCs soma.…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, Ccdc134 loss leads to severe hemorrhages in the brain ventricular space and neural tube. 14 Thus, we hypothesize that CCDC134 might be critical for brain development.…”

Section: Introductionmentioning

confidence: 98%

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Ccdc134 deficiency impairs cerebellar development and motor coordination

Yin

Liao

Wang

et al. 2021

Genes Brain and Behavior

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Coiled-coil domain containing 134 (CCDC134) has been shown to serve as an immune cytokine to exert antitumor effects and to act as a novel regulator of hADA2a to affect PCAF acetyltransferase activity. While Ccdc134 loss causes abnormal brain development in mice, the significance of CCDC134 in neuronal development in vivo is controversial. Here, we report that CCDC134 is highly expressed in Purkinje cells (PCs) at all developmental stages and regulates mammalian cerebellar development in a cell type-specific manner. Selective deletion of Ccdc134 in mouse neural stem cells (NSCs) caused defects in cerebellar morphogenesis, including a decrease in the number of PCs and impairment of PC dendritic growth, as well as abnormal granule cell development. Moreover, loss of Ccdc134 caused progressive motor dysfunction with deficits in motor coordination and motor learning. Finally, Ccdc134 deficiency inhibited Wnt signaling but increased Ataxin1 levels. Our findings provide evidence that CCDC134 plays an important role in cerebellar development, possibly through regulating Wnt signaling and Ataxin1 expression levels, and in controlling cerebellar function for motor coordination and motor learning, ultimately making it a potential contributor to cerebellar pathogenesis.

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CCDC134 serves a crucial role in embryonic development

Cited by 12 publications

References 34 publications

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

CCDC134 as a Prognostic-Related Biomarker in Breast Cancer Correlating With Immune Infiltrates

Ccdc134 deficiency impairs cerebellar development and motor coordination

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