Role of CITED2 in stem cells and cancer (Review)

An, Beiying; Ji, Xufeng; Yang, Gong

doi:10.3892/ol.2020.11968

Cited by 12 publications

(12 citation statements)

References 116 publications

(191 reference statements)

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“…Zhou et al identified ANKZF1 as a prognostic biomarker in colon cancer, and overexpression of ANKZF1 could predict poor OS and recurrence-free survival ( Zhou et al, 2019 ; Chen et al, 2020 ). CITED2 is highly expressed in many malignancies, including breast cancer, lung cancer, colon cancer and gastric cancer, and it plays critical roles in cancer metastasis and invasiveness ( An et al, 2020 ). In addition, CITED2 is a direct product of HIF-mediated transcription and acts as a vital regulator of stem cell transcription factors in cancer stem-like cells ( Rasti et al, 2018 ; Usui-Ouchi et al, 2020 ), suggesting that targeting CITED2 expression might be a novel therapeutic strategy for cancer treatment and relapse prevention.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

et al. 2022

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Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive and fatal gastrointestinal malignancies with high morbidity and mortality worldwide. Accumulating evidence has revealed the clinical significance of the interaction between the hypoxic microenvironment and cancer stemness in pancreatic cancer progression and therapies. This study aims to identify a hypoxia-stemness index-related gene signature for risk stratification and prognosis prediction in PAAD.Methods: The mRNA expression-based stemness index (mRNAsi) data of PAAD samples from The Cancer Genome Atlas (TCGA) database were calculated based on the one-class logistic regression (OCLR) machine learning algorithm. Univariate Cox regression and LASSO regression analyses were then performed to establish a hypoxia-mRNAsi-related gene signature, and its prognostic performance was verified in both the TCGA-PAAD and GSE62452 corhorts by Kaplan-Meier and receiver operating characteristic (ROC) analyses. Additionally, we further validated the expression levels of signature genes using the TCGA, GTEx and HPA databases as well as qPCR experiments. Moreover, we constructed a prognostic nomogram incorporating the eight-gene signature and traditional clinical factors and analyzed the correlations of the risk score with immune infiltrates and immune checkpoint genes.Results: The mRNAsi values of PAAD samples were significantly higher than those of normal samples (p < 0.001), and PAAD patients with high mRNAsi values exhibited worse overall survival (OS). A novel prognostic risk model was successfully constructed based on the eight-gene signature comprising JMJD6, NDST1, ENO3, LDHA, TES, ANKZF1, CITED, and SIAH2, which could accurately predict the 1-, 3-, and 5-year OS of PAAD patients in both the training and external validation datasets. Additionally, the eight-gene signature could distinguish PAAD samples from normal samples and stratify PAAD patients into low- and high-risk groups with distinct OS. The risk score was closely correlated with immune cell infiltration patterns and immune checkpoint molecules. Moreover, calibration analysis showed the excellent predictive ability of the nomogram incorporating the eight-gene signature and traditional clinical factors.Conclusion: We developed a hypoxia-stemness-related prognostic signature that reliably predicts the OS of PAAD. Our findings may aid in the risk stratification and individual treatment of PAAD patients.

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Section: Discussionmentioning

confidence: 99%

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

et al. 2022

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“…We next examined the potential cell-autonomous actions of CITED2 on junctional zone development. CITED2 is a known transcriptional co-regulator [15][16][17] , which prompted an examination of CITED2 deficiencies on the junctional zone gene regulatory network. RNA sequencing (RNA-seq) was performed on gd 14.5 wild type and Cited2 null junctional zone tissues.…”

Section: Cited2 Deficiency Affects Gene Regulatory Network In the Jun...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Understanding cellular decision-making within the EVT cell column and junctional zone provides insights into the development of the invasive trophoblast cell lineage. CBP/p300 interacting transactivator, with Glu/Asp-rich carboxy terminal domain, 2 (CITED2) is a transcriptional co-regulator possessing the capacity to modulate interactions between DNA binding proteins and histone modifying enzymes, specifically transcription factor-CREB binding protein (CREBBP or CBP)/EIA binding protein p300 (EP300) interactions (15)(16)(17). CBP and EP300 possess histone 3 lysine 27 (H3K27) acetyl transferase activity (18,19) and have been implicated in trophoblast cell differentiation and their dysregulation linked to diseases of the placenta, including preeclampsia and intrauterine growth restriction (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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CITED2 is a Conserved Regulator of the Uterine-Placental Interface

Kuna

Dhakal

Iqbal

et al. 2022

Preprint

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Establishment of the hemochorial placentation site requires the exodus of trophoblast cells from the placenta and their transformative actions on the uterine vasculature, which is a critical but poorly understood developmental process. CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl terminal domain 2 (CITED2) is a member of the CITED protein family of co-regulators and has been shown to possess roles in embryogenesis, including placenta development. We examined the involvement of CITED2 in the rat, which exhibits deep hemochorial placentation, a feature it shares with the human. CITED2 is distinctively expressed in the junctional zone compartment of the rat placentation site and in intrauterine invasive trophoblast cells. Homozygous disruption of the rat Cited2 locus resulted in placental and fetal growth restriction and abnormalities in heart and lung development, which are also characteristic of the CITED2 deficient mouse model. However, other features of the mouse Cited2 null phenotype, including exencephaly, adrenal gland agenesis, and prenatal lethality were not associated with CITED2 deficiency in the rat. Trophoblast-specific lentiviral CITED2 knockdown in the rat yielded a growth arrested placental phenotype. Smaller Cited2 null placentas were associated with a growth restricted junctional zone and coincided with a delay in intrauterine trophoblast cell invasion. Invasive trophoblast cells arise from the junctional zone. Transcriptomes of the junctional zone, the invasive trophoblast cell lineage, and differentiating trophoblast stem cells were affected by CITED2 disruption, as were placental adaptations to hypoxia and exposure to viral mimetics. Evidence for the conservation of CITED2 expression in human placental tissue and conserved actions in invasive/extravillous trophoblast cell development were demonstrated. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.

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“…This protein has CAD and NAD terminals (Bhattacharya et al, 1999). Furthermore, this protein regulates the transcription of TFAP2, SMAD2, estrogen receptor, and hypoxiainducible factor 1 (17).…”

Section: Introductionmentioning

confidence: 99%

Missense Mutations in the CITED2 Gene Contribute to Congenital Heart Disease

Yaqoob,

Ahmad

2024

Preprint

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Background Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients. Methods A total of 350 samples were collected 250 from patients and 100 from controls for genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing. Results The frequency of the homozygous mutant (CC) in CHD patients was 48.4% and of heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, which is greater than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous and the results were like as those obtained through conventional PCR. Conclusion CHD patient’s samples showed mutations. Therefore, it can say that CITED2 gene SNP might be associated with CHD.

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Role of CITED2 in stem cells and cancer (Review)

Cited by 12 publications

References 116 publications

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

CITED2 is a Conserved Regulator of the Uterine-Placental Interface

Missense Mutations in the CITED2 Gene Contribute to Congenital Heart Disease

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