The<i>in vitro</i>and<i>in vivo</i>effects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target

Zheng, Haixue; Liu, Jiajie; Li, Jing; Wu, Jicheng; Yang, Lei; Zhao, Guifeng; Zhao, Xin; Jiang, Huamao; Huang, Kejie; Li, Zhijie

doi:10.18632/oncotarget.15377

Cited by 7 publications

(14 citation statements)

References 25 publications

(32 reference statements)

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“…However, Shen et al [ 17 ] found parafibromin expression was inversely associated with the differentiation of ovarian cancers. Recently, we reported that CDC73 expression was higher in moderately- than well-differentiated adenocarcinoma at both mRNA and protein level [ 29 ], opposite to our finding. As a differentiation marker, ALP activity was increased in CDC73 transfectants of colorectal cancer cells [ 13 , 29 ].…”

Section: Discussioncontrasting

confidence: 99%

“…Recently, we reported that CDC73 expression was higher in moderately- than well-differentiated adenocarcinoma at both mRNA and protein level [ 29 ], opposite to our finding. As a differentiation marker, ALP activity was increased in CDC73 transfectants of colorectal cancer cells [ 13 , 29 ]. Taken together, we concluded that CDC73 mRNA underlay the molecular mechanisms of the differentiation of gastric cancer.…”

Section: Discussioncontrasting

confidence: 99%

“…Parafibromin protein was found in the cilia of pseudo-stratified bronchial and fallopian epithelium [ 16 , 17 ]. In our previous work [ 29 ], WT parafibromin overexpression was found to suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells, but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin. According to transcriptomic analysis, WT parafibromin suppressed PI3K-Akt and FoxO signaling pathways, while MT one promoted PI3K-Akt pathway, focal adhesion, and regulation of actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

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The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis

2017

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CDC73 interacts with human PAF1 complex, histone methyltransferase complex and RNA polymerase II for transcription elongation and 3’ end processing. Its down-regulated expression was immunohistochemically detected in gastric, colorectal, ovarian and head and neck cancers, and positively correlated with aggressive behaviors and unfavorable prognosis of malignancies. We performed a bioinformatics analysis by using Oncomine, TCGA and KM plotter databases. It was found that CDC73 mRNA was overexpressed in gastric, lung, breast and ovarian cancers, even stratified by histological subtypes (p<0.05). CDC73 mRNA expression was stronger in gastric intestinal- than diffuse-type carcinomas (p<0.05), and positively correlated with distant metastasis and TNM staging of lung cancer (p<0.05). CDC73 mRNA expression was positively related to both overall and progression-free survival rates of the patients with gastric cancer, even stratified by gender, lymph node involvement, or treatment (p<0.05), while versa for breast cancer (p<0.05). The prognostic significance of CDC73 mRNA was dependent on the datasets and pathological grouping in lung and ovarian cancers. These findings indicated the CDC73 mRNA overexpression was positively linked to carcinogenesis. It is cautious to employ CDC73 mRNA to evaluate the clinicopathological behaviors and prognosis of cancers.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis

2017

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“…Previously, we determined the parafibromin profiles and their clinicopathological significances in head and neck, lung, gastric, colorectal, and ovarian cancers. The downregulated expression of parafibromin in the above-mentioned cancers was negatively correlated with their aggressive variables and adverse prognosis ( Zheng et al, 2011 ; Shen et al, 2016 ; Zhu et al, 2016 ; Zheng et al, 2017a ; Zheng et al, 2017b ). In breast cancer, parafibromin expression was inversely correlated with T stage, clinicopathological stage, local lymphovascular invasion, and C-erbB2 expression ( Selvarajan et al, 2008 ).…”

Section: Introductionmentioning

confidence: 98%

The roles of the tumor suppressor parafibromin in cancer

Zheng

Xue

Zhang³

2022

Front. Cell Dev. Biol.

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In this review, we discuss parafibromin protein, which is encoded by CDC73. A mutation in this gene causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disease. CDC73 is transcriptionally downregulated by the Wilms’ tumor suppressor gene WT1 and translationally targeted by miR-182-3p and miR-155. In the nucleus, parafibromin binds to RNA polymerase II and PAF1 complex for transcription. Parafibromin transcriptionally increases the expression of c-Myc, decreases CPEB1 expression by interacting with H3M4, and reduces cyclin D1 expression by binding to H3K9. The RNF20/RNF40/parafibromin complex induces monoubiquitination of H2B-K120, and SHP2-mediated dephosphorylation of parafibromin promotes the parafibromin/β-catenin interaction and induces the expression of Wnt target genes, which is blocked by PTK6-medidated phosphorylation. Parafibromin physically associates with the CPSF and CstF complexes that are essential for INTS6 mRNA maturation. In the cytosol, parafibromin binds to hSki8 and eEF1Bγ for the destabilization of p53 mRNA, to JAK1/2-STAT1 for STAT1 phosphorylation, and to actinin-2/3 to bundle/cross-link actin filaments. Mice with CDC73 knockout in the parathyroid develop parathyroid and uterine tumors and are used as a model for HPT-JT syndrome. Conditional deletion of CDC73 in mesenchymal progenitors results in embryos with agenesis of the heart and liver while its abrogation in mature osteoblasts and osteocytes increases cortical and trabecular bone. Heterozygous germline mutations in CDC73 are associated with parathyroid carcinogenesis. The rates of CDC73 mutation and parafibromin loss decrease from parathyroid adenoma to atypical adenoma to carcinoma. In addition, down-regulated parafibromin is closely linked to the tumorigenesis, subsequent progression, or poor prognosis of head and neck, gastric, lung, colorectal, and ovarian cancers, and its overexpression might reverse the aggressiveness of these cancer cells. Therefore, parafibromin might be useful as a biological marker of malignancies and a target for their gene therapy.

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“…Han et al 9 found that inhibiting the expression of transcription factor sp1 can promote the apoptosis of CRC cells and the arrest of cell cycle, thereby inhibiting the proliferation of CRC. Zheng et al 10 found that the overexpression of parafibromin (the cell division cycle protein) can inhibit the progression of CRC division. Chen et al 11 found that the over-expressed ribosomal protein S15A can induce malignant transformation of CRC cells through the p53 signaling pathway, consequently resulting in erroneous regulation of the p53 signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Mining the key genes regulating colorectal cancer proliferation based on the GEO database

Zhao

Chen

et al. 2020

Preprint

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Colorectal cancer (CRC) is a common tumor in digestive system with high morbidity and mortality. In this work, three datasets (GSE68468, GSE21510, and GSE9348) were selected from the public GEO database, and the deferentially expressed genes (DEGs) related to CRC were screened out by bioinformatics approach. The GO (gene ontology) analysis on DEGs was carried out and followed by the KEGG (kyoto encyclopedia of genes and genomes) analysis. Finally, protein-protein interaction (PPI) networks of DEGs were respectively constructed by using the STRING database. Our results showed that a total of 849 DEGs in common were identified from the three datasets, including 406 up-regulated genes and 443 down-regulated genes. The GO analysis demonstrated that the DEGs are mainly related to cell division, cell proliferation, cell signaling, and immune response. The KEGG analysis revealed that DEGs are mainly enriched in cell cycle and cell signaling pathway. Based on the PPI network analysis, we identified a total of 86 key genes: 72 up-regulated genes mainly consist of CD and KIF genes while 14 down-regulated genes are mainly composed of various members of CC genes. In particular, we found that the CRC proliferation should be enhanced by the interaction of CDK1 with CDKN3 and KIF15. On the one hand, CRC proliferation is enhanced by over-expressing the CD and KIF genes involving in cell division and cell proliferation. On the other hand, CRC proliferation is strengthened through silencing the expression of the CC genes associated with immune response.

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Thein vitroandin vivoeffects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target

Cited by 7 publications

References 25 publications

The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis

The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis

The roles of the tumor suppressor parafibromin in cancer

Mining the key genes regulating colorectal cancer proliferation based on the GEO database

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