TIMELESS contributes to the progression of breast cancer through activation of MYC

Chi, Limin; Zou, Yujiao; Qin, Ling; Ma, Wenxue; Hao, Yanyan; Tang, Yao; Luo, Rong; Wu, Ziqing

doi:10.1186/s13058-017-0838-1

Cited by 37 publications

(43 citation statements)

References 36 publications

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“…A recent study confirmed that TIMELESS levels in both breast cancer cell lines and tissues were significantly over-expressed. Upregulation of TIMELESS dramatically enhanced, while knockdown of TIMELESS suppressed the self-renewal of cancer stem cells (CSCs), cell invasion and migration abilities of breast cancer cells in vitro [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Lesicka¹,

Jabłońska²,

Wieczorek³

et al. 2018

PLoS ONE

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Breast cancer has a multifactorial etiology. One of the supposed and novel mechanisms is an alteration of circadian gene expression. Circadian genes play a crucial role in many physiological processes. These processes, such as genomic stability, DNA repair mechanism and apoptosis, are frequently disrupted in breast tumors. To assess the significance of circadian gene expression in breast cancer, we carried out an analysis of CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1, CRY2, TIMELESS, CSNK1E expression by the use of the quantitative Real-Time PCR technique in tumor tissue and non-tumor adjacent normal tissue sampled from 107 women with a newly diagnosed disease. The obtained data were compared to the clinical and histopathological features. PER1, PER2, PER3, CRY2 were found to be significantly down-expressed, while CLOCK, TIMELESS were over-expressed in the studied tumor samples compared to the non-tumor samples. Only gene expression of CRY1 was significantly down-regulated with progression according to the TNM classification. We found significantly decreased expression of CRY2, PER1, PER2 genes in the ER/PR negative breast tumors compared to the ER/PR positive tumors. Additionally, expression of CRY2, NPAS2 genes had a decreased level in the poorly differentiated tumors in comparison with the well and moderately differentiated ones. Our results indicate that circadian gene expression is altered in breast cancer tissue, which confirms previous observations from various animal and in vitro studies.

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Section: Discussionmentioning

confidence: 99%

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Lesicka¹,

Jabłońska²,

Wieczorek³

et al. 2018

PLoS ONE

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“…Tim functions in cell cycle progression, DNA replication, DNA damage response, and telomere length and integrity maintenance 29 , making it a multifaceted factor implicated in aging and death. Tim has drawn more and more attention in recent studies for its role in cancer 30 – 32 , also indicates its versatility. It also raises the possibility that immune response towards infection is one of the underlying reasons, given that the role of tim as a regulator of immune response has been recently revealed in Planarian 33 .…”

Section: Discussionmentioning

confidence: 99%

Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster

Zhao

Warman

Cheeseman

2018

Sci Rep

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The importance of the circadian clock for the regulation of behaviour and physiology, and the molecular control of these rhythms by a set of clock genes are well defined. The circadian clock deteriorates with advancing age but the mechanism underlying is unclear. Here we recorded the expression of two key clock genes in young, middle-aged and old Drosophila using transgenic luciferase lines reporting period and timeless in vivo. We report a novel marker of imminent death in the expression of TIMELESS. In the days immediately preceding death TIMELESS expression increased to at least 150% of previous acrophase values (88.0% of n = 217) and lost circadian rhythmicity, which predicted death equally well in flies of different ages and under light and temperature cycles. We suggest this transient aberrant clock-gene expression is central to the mechanism of the disturbance in circadian behaviour before death (82.7% of n = 342). We also find that PERIOD expression in central-clock neurons remained robust with age, however PERIOD and TIMELESS in peripheral clocks showed a reduction in both expression level and rhythmicity. In conclusion, as flies age the molecular clock gradually declines at the peripheral level but continues to function at the central until days before death.

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“… 14 – 19 TIMELESS contributes to the progression of breast cancer through activation of MYC. 20 TIMELESS forms a complex with PARP1 and plays a role in the DNA damage response. 21 One study has reported that overexpression of TIMELESS in NPC cell lines results in resistance to cisplatin-induced apoptosis in vitro and in vivo via the Wnt/β-catenin pathway and downstream gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Identification of driver genes associated with chemotherapy resistance of Ewing’s sarcoma

Liao

Xie

et al. 2018

OTT

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BackgroundThe aim of this study was to identify the driver genes associated with chemotherapy resistance of Ewing’s sarcoma and potential targets for Ewing’s sarcoma treatment.MethodsTwo mRNA microarray datasets, GSE12102 and GSE17679, were downloaded from the Gene Expression Omnibus database, which contain 94 human Ewing’s sarcoma samples, including 65 from those who experienced a relapse and 29 from those with no evidence of disease. The differen tially expressed genes (DEGs) were identified using LIMMA package R. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for DEGs using Database for Annotation, Visualization and Integrated Analysis. The protein–protein interaction network was constructed using Cytoscape software, and module analysis was performed using Molecular Complex Detection.ResultsA total of 206 upregulated DEGs and 141 downregulated DEGs were identified. Upregulated DEGs were primarily enriched in DNA replication, nucleoplasm and protein kinase binding for biological processes, cellular component and molecular functions, respectively. Downregulated DEGs were predominantly involved in receptor clustering, membrane raft, and ligand-dependent nuclear receptor binding. The protein–protein interaction network of DEGs consisted of 150 nodes and 304 interactions. Thirteen hub genes were identified, and biological analysis revealed that these genes were primarily enriched in cell division, cell cycle, and mitosis. Furthermore, based on closeness centrality, betweenness centrality, and degree centrality, the three most significant genes were identified as GAPDH, AURKA, and EHMT2. Furthermore, the significant network module was composed of nine genes. These genes were primarily enriched in mitotic nuclear division, mitotic chromosome condensation, and nucleoplasm.ConclusionThese hub genes, especially GAPDH, AURKA, and EHMT2, may be closely associated with the progression of Ewing’s sarcoma chemotherapy resistance, and further experiments are needed for confirmation.

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TIMELESS contributes to the progression of breast cancer through activation of MYC

Cited by 37 publications

References 36 publications

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster

Identification of driver genes associated with chemotherapy resistance of Ewing’s sarcoma

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TIMELESS contributes to the progression of breast cancer through activation of MYC

Cited by 37 publications

References 36 publications

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster

Identification of driver genes associated with chemotherapy resistance of Ewing&rsquo;s sarcoma

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Identification of driver genes associated with chemotherapy resistance of Ewing’s sarcoma