Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells

Sun, Ziyi; Pan, Xia; Zou, Zhenwei; Ding, Qi; Wu, Gang; Peng, Gang

doi:10.1186/s13014-015-0445-1

Cited by 15 publications

(10 citation statements)

References 33 publications

(45 reference statements)

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“…The right-hand panel is an enlarged view of the left-hand panel 5% of BC. We found that KDM4C and PTPN6 have been shown to regulate CS in human cell lines, and will be added to build 2 of CellAge [65,66].…”

Section: Unweighted Rna-seq Co-expression Networkmentioning

confidence: 98%

A multidimensional systems biology analysis of cellular senescence in aging and disease

et al. 2020

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Background: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Conclusions: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

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Section: Unweighted Rna-seq Co-expression Networkmentioning

confidence: 98%

A multidimensional systems biology analysis of cellular senescence in aging and disease

et al. 2020

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“…and PTPN6 have been shown to regulate CS in human cell lines, and will be added to build 2 of CellAge (Sun et al, 2015;Yu et al, 2018).…”

Section: Unweighted Rna-seq Co-expression Networkmentioning

confidence: 99%

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

Avelar

Ortega

Tăcutu

et al. 2019

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Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses. We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases.By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes.Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

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“…In addition, there have been few reports regarding the role of senescence in NPC. For example, evidence indicates that CDDP induces senescence in NPC cells, resulting in cell growth arrest ( 14 ), and a high expression of SHP-1 can inhibit cellular senescence to induce radiotherapeutic resistance in NPC ( 15 ). However, the molecular mechanisms through which senescence participates in chemoresistance in NPC are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma

et al. 2018

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Resistance to radiotherapy and chemotherapy currently represents one of the major reasons for therapeutic failure in nasopharyngeal carcinoma (NPC). However, the mechanisms underlying resistance to chemotherapy in NPC remain unclear. In this study, cell counting assay, cell cycle assay and senescence associated β-galactosidase activity were performed to evaluate cell growth, proliferation and senescence, respectively. We found that the aberrant expression of cyclooxygenase-2 (COX-2) was associated with a poor outcome and recurrance in patients with NPC. In NPC cells, COX-2 overexpression increased cell proliferation, inhibited cellular senescence and resulted in chemoresistance, while the knockdown of COX-2 reduced cell proliferation, promoted cellular senescence and overcame chemoresistance. Furthermore, fibroblasts from COX-2 knockout mice exhibited cellular senescence, particularly when treated with chemotherapeutic agents. Mechanistically, COX-2 interacted with p53 protein and inhibited cellular senescence, which resulted in chemotherapeutic resistance. On the whole, these findings indicate that COX-2 may play a critical role in chemotherapeutic resistance in NPC via the inhibition of chemotherapy-induced senescence via the inactivation of p53. This study provides experimental evidence for the preclinical value of increasing chemotherapy-induced senescence by targeting COX-2 as an effective antitumor treatment in patients with recurrent NPC.

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Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells

Cited by 15 publications

References 33 publications

A multidimensional systems biology analysis of cellular senescence in aging and disease

A multidimensional systems biology analysis of cellular senescence in aging and disease

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma

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