Centromere Protein N Participates in Cellular Proliferation of Human Oral Cancer by Cell-Cycle Enhancement

Oka, Noritoshi; Kasamatsu, Atsushi; Endo‐Sakamoto, Yosuke; Eizuka, Keitaro; Wagai, Sho; Koide-Ishida, Nao; Miyamoto, Isao; Iyoda, Manabu; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.7150/jca.32281

Cited by 22 publications

(26 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Rahman et al (2019) identified CENPN as a poor prognostic marker for colorectal cancer by bioinformatics analysis. Recently, it was reported that CENPN can promote the proliferation of oral cancer cells in the entrance cavity by regulating the cell cycle ( Oka et al, 2019 ). However, the expression of CENPN in HCC and its role and mechanism in malignant development are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The inactivation of these complexes results in other proteins not being phosphorylated, including pRb (RB1), so it is unable to release E2F transcription factors to activate the expression of genes that regulate S phase (Matsuoka et al, 1994). Previous research has revealed that the negative regulation of cyclin D1 and CDK4 is consistent with the downregulation of CENPN (Molenaar et al, 2008), and recent reports in oral squamous cell carcinoma (OSCC) suggest that downregulation of CENPN can reduce the expression of cyclin D1 and CDK4 with corresponding increases in the expression of p21 and p27 (Oka et al, 2019). This suggests that interfering with CENPN expression in OSCC can upregulate p27 and p21 expression to inhibit CDK4 and cyclin D1 expression and arrest the cell cycle in G1 phase.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma

Wang¹,

Yu²,

Zheng

et al. 2021

PeerJ

View full text Add to dashboard Cite

Background Hepatocellular carcinoma (HCC) is one of the deadliest tumors. The majority of HCC is detected in the late stage, and the clinical results for HCC patients are poor. There is an urgent need to discover early diagnostic biomarkers and potential therapeutic targets for HCC. Methods The GSE87630 and GSE112790 datasets from the Gene Expression Omnibus (GEO) database were downloaded to analyze the differentially expressed genes (DEGs) between HCC and normal tissues. R packages were used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the DEGs. A Search Tool for Retrieval of Interacting Genes (STRING) database was used to develop a protein-protein interaction (PPI) network, and also cytoHubba, Molecular Complex Detection (MCODE), EMBL-EBI, CCLE, Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine analyses were performed to identify hub genes. Gene expression was verified with a third GEO dataset, GSE25097. The Cancer Genome Atlas (TCGA) database was used to explore the correlations between the hub genes and clinical indexes of HCC patients. The functions of the hub genes were enriched by gene set enrichment analysis (GSEA), and the biological significance of the hub genes was explored by real-time polymerase chain reaction (qRT-PCR), western blot, immunofluorescence, CCK-8, colony formation, Transwell and flow cytometry assays with loss-of-function experiments in vitro. Results Centromere protein N (CENPN) was screened as a hub gene affecting HCC tumorigenesis. Evaluation by Cox regression showed that a high level of CENPN expression was an independent danger variable for poor prognosis of HCC. GSEA showed that high CENPN expression was linked to the following pathways: liver cancer subclass proliferation, cell cycle, p53 signaling pathway, Rb1 pathway, positive regulation of cell cycle G1/S phase transition, and DNA damage response signal transduction by p53 class moderators. Further cell experiments showed that knocking down CENPN expression decreased the proliferation and colony-forming abilities of HepG2 and Huh7 cells as well as Ki67 expression in these cell lines. The cell cycle was arrested in G1 phase, which is consistent with previous experiments on CENPN downregulation., but neither migration nor invasion were significantly affected. Western blot results revealed that the expression of p53, p27, p21, CDK4, cyclin D1, CDK2, cyclin E, pRb, E2F1 and c-myc decreased after CENPN knockdown, but there was no significant change in total Rb levels. In addition, CENPN-knockdown cells subjected to irradiation showed significantly enhanced of γ-H2AX expression and reduced colony formation. Conclusion CENPN functions as an oncogene in HCC and may be a therapeutic target and promising prognostic marker for HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma

Wang¹,

Yu²,

Zheng

et al. 2021

PeerJ

View full text Add to dashboard Cite

show abstract

“…(22) As previous studies reported, other Centrome protein such as CENPN knockdown (shCENP-N) cells showed depressed cellular proliferation by cell-cycle arrest at the G1 phase with up-regulation of p21Cip1 and p27Kip1 and down-regulation of cyclin D1, CDK2, and CDK4. (23) The mechanism of CENPO in cancer was insu cient, our research rstly demonstrated that CENPO may affect apoptosis related protein, cell cycle related proteins and PI3K/AKT/mTOR signaling thus regulated many malignant behaviors such as proliferation, apoptosis, cellcycle thus promoting the progression of NSCLC. However, whether these relationship had connected relationship or cross taking.…”

Section: Discussionmentioning

confidence: 89%

The role of CENPO expression in the progression of non-small cell lung cancer

Yang

Chen

Sun

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The role of Centromere protein O (CENPO) in the development of non-small cell lung cancer (NSCLC) is unknown. This study aimed to investigate the potential roleof CENPO in the development of NSCLCMethods: The expression level of CENPO was investigated in both tissues and cell-lines. Celigo cell counting assay, wound-healing assay, Transwell assay and Flow cytometry was used to explore the effect of CENPO on proliferation, migration, invasion, apoptosis and cell cycle of NSCLC. The potential mechanism of CENPO was explored by Human Apoptosis Antibody, also, western blot was conducted to detect the expression of PI3K/Akt/mTOR pathway and cell-cycle related protein (mTOR, P-mTOR, CDK1, CDK6 and PIK3CA). Besides, the effect of CENPO on the growth of NSCLC solid tumors was demonstrated in vivo.Results: Our study suggested CENPO gene overexpression in NSCLC. Reduced CENPO expression substantially decreased the proliferation, migration and invasion ability, and promoting apoptosis and induces cell cycle arrest of NSCLC cell-lines. Preliminary mechanism research suggested reduced CENPO could active apoptosis pathway, suppressing PI3K/AKT/mTOR pathway and down-regulation cell-cycle related proteins.Conclusion: CENPO was up-regulated in NSCLC and played an important role in promoting the progress of NSCLC.

show abstract

“…CENP-N plays an essential role in cell cycle progression and cell mitosis [33,41]. Localization of CENP-N in different cell phases and incorrect congression and segregation of chromosomes by depletion of CENP-N in silkworms have uncovered its kinetochore function.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms

Lü

et al. 2019

IJMS

View full text Add to dashboard Cite

The centromere, in which kinetochore proteins are assembled, plays an important role in the accurate congression and segregation of chromosomes during cell mitosis. Although the function of the centromere and kinetochore is conserved from monocentric to holocentric, the DNA sequences of the centromere and components of the kinetochore are varied among different species. Given the lack of core centromere protein A (CENP-A) and CENP-C in the lepidopteran silkworm Bombyx mori, which possesses holocentric chromosomes, here we investigated the role of CENP-N, another important member of the centromere protein family essential for kinetochore assembly. For the first time, cellular localization and RNA interference against CENP-N have confirmed its kinetochore function in silkworms. To gain further insights into the regulation of CENP-N in the centromere, we analyzed the affinity-purified complex of CENP-N by mass spectrometry and identified 142 interacting proteins. Among these factors, we found that the chaperone protein heat shock cognate 70 (HSC70) is able to regulate the stability of CENP-N by prohibiting ubiquitin–proteasome pathway, indicating that HSC70 could control cell cycle-regulated degradation of CENP-N at centromeres. Altogether, the present work will provide a novel clue to understand the regulatory mechanism for the kinetochore activity of CENP-N during the cell cycle.

show abstract

Centromere Protein N Participates in Cellular Proliferation of Human Oral Cancer by Cell-Cycle Enhancement

Cited by 22 publications

References 34 publications

Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma

Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma

The role of CENPO expression in the progression of non-small cell lung cancer

Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms

Contact Info

Product

Resources

About