DEK terminates diapause by activation of quiescent cells in the crustacean Artemia

2019 ◽  
Vol 476 (12) ◽  
pp. 1753-1769
Author(s):  
Wen-Huan Jia ◽  
An-Qi Li ◽  
Jing-Yi Feng ◽  
Yan-Fu Ding ◽  
Sen Ye ◽  
...  
Keyword(s):  
Rna Sequences ◽  
Quiescent Cells ◽  
P53 Signaling ◽  
Cellular Events ◽  
Short Period ◽  
Cell Quiescence ◽  
Cellular Quiescence ◽  
P53 Signaling Pathway ◽  
Insight Into ◽  
Mcf 7

Abstract To cope with harsh environments, the Artemia shrimp produces gastrula embryos in diapause, a state of obligate dormancy, having cellular quiescence and suppressed metabolism. The mechanism behind these cellular events remains largely unknown. Here, we study the regulation of cell quiescence using diapause embryos of Artemia. We found that Artemia DEK (Ar-DEK), a nuclear factor protein, was down-regulated in the quiescent cells of diapause embryos and enriched in the activated cells of post-diapause embryos. Knockdown of Ar-DEK induced the production of diapause embryos whereas the control Artemia released free-swimming nuaplii. Our results indicate that Ar-DEK correlated with the termination of cellular quiescence via the increase in euchromatin and decrease in heterochromatin. The phenomena of quiescence have many implications beyond shrimp ecology. In cancer cells, for example, knockdown of DEK also induced a short period of cellular quiescence and increased resistance to environmental stress in MCF-7 and MKN45 cancer cell lines. Analysis of RNA sequences in Artemia and in MCF-7 revealed that the Wnt and AURKA signaling pathways were all down-regulated and the p53 signaling pathway was up-regulated upon inhibition of DEK expression. Our results provide insight into the functions of Ar-DEK in the activation of cellular quiescence during diapause formation in Artemia.

scholarly journals Exploring the Mechanism of Baicalin Intervention in Breast Cancer Based on MicroRNA Microarrays and Bioinformatics Strategies

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Anqi Ge ◽  
Lifang Liu ◽  
Xian’guang Deng ◽  
Jun Luo ◽  
Yanghua Xu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Enrichment Analysis ◽  
Dependent Manner ◽  
P53 Signaling ◽  
Microrna Microarrays ◽  
P53 Signaling Pathway ◽  
Mcf 7

Objective. To explore the mechanism of baicalin intervention in breast cancer based on microRNA microarrays. Methods. The inhibitory rate of baicalin intervention in MCF-7 breast cancer cells was determined by MTT. Then, the miRNA microarrays were used to validate the key microRNAs. After that, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate microRNA, hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-miR-7t. Finally, the potential targets of these key microRNAs are predicted by miRWalk, and DAVID was utilized for gene ontology (GO) enrichment analysis and pathway enrichment analysis. Results. Baicalin may inhibit the proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. The concentration of baicalin 150 μmol/L was determined for the subsequent miRNA chip research. A total of 92 upregulated microRNAs and 35 downregulated microRNAs were obtained. The upregulated miRNAs include hsa-miR-6799-5p, hsa-miR-6126, hsa-miR-4792, hsa-miR-6848-5p, hsa-miR-3197, hsa-miR-6779-5p, and hsa-miR -654-5p. The downregulated miRNAs include hsa-miR-3911, hsa-miR-504-5p, hsa-miR-30a-3p, hsa-miR-193b-3p, and hsa-miR-181b-5p. Then, differentially expressed miRNA was verified by qRT-PCR. The results showed that the expression of hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-let-7c was upregulated ( P < 0.05 ), which was consistent with the results of the miRNA microarray. The enrichment analysis showed that baicalin might regulate the DNA-templated proliferation, DNA-templated transcription, p53 signaling pathway, etc., of MCF-7 breast cancer cells through miRNA. Conclusion. Baicalin inhibits the proliferation of breast cancer cells. It may achieve antitumor effects through regulating microRNAs so as to affect the DNA replication (such as cellular response to DNA damage stimulus and DNA binding), RNA transcription (such as regulation of transcription, DNA-templated, transcription from RNA polymerase II promoter, and transcription factor binding), protein synthesis (such as mRNA binding, Golgi apparatus, and protein complex), endocytosis, pathways in cancer, p53 signaling pathway, and so on.

scholarly journals Mechanisms that Link Chronological Aging to Cellular Quiescence in Budding Yeast

2020 ◽  
Vol 21 (13) ◽  
pp. 4717
Author(s):  
Karamat Mohammad ◽  
Jennifer Anne Baratang Junio ◽  
Tala Tafakori ◽  
Emmanuel Orfanos ◽  
Vladimir I. Titorenko
Keyword(s):  
Caloric Restriction ◽  
Budding Yeast ◽  
Yeast Cells ◽  
Yeast Culture ◽  
Chronological Aging ◽  
Quiescent Cells ◽  
Cellular Events ◽  
Age Related ◽  
Calorie Diet ◽  
Cellular Quiescence

After Saccharomyces cerevisiae cells cultured in a medium with glucose consume glucose, the sub-populations of quiescent and non-quiescent cells develop in the budding yeast culture. An age-related chronology of quiescent and non-quiescent yeast cells within this culture is discussed here. We also describe various hallmarks of quiescent and non-quiescent yeast cells. A complex aging-associated program underlies cellular quiescence in budding yeast. This quiescence program includes a cascade of consecutive cellular events orchestrated by an intricate signaling network. We examine here how caloric restriction, a low-calorie diet that extends lifespan and healthspan in yeast and other eukaryotes, influences the cellular quiescence program in S. cerevisiae. One of the main objectives of this review is to stimulate an exploration of the mechanisms that link cellular quiescence to chronological aging of budding yeast. Yeast chronological aging is defined by the length of time during which a yeast cell remains viable after its growth and division are arrested, and it becomes quiescent. We propose a hypothesis on how caloric restriction can slow chronological aging of S. cerevisiae by altering the chronology and properties of quiescent cells. Our hypothesis posits that caloric restriction delays yeast chronological aging by targeting four different processes within quiescent cells.

The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

2020 ◽  
Vol 15 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Ijaz Muhammad ◽  
Noor Rahman ◽  
Gul E. Nayab ◽  
Sadaf Niaz ◽  
Mohibullah Shah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cancer Therapy ◽  
Natural Product ◽  
Signaling Pathway ◽  
In Silico ◽  
P53 Protein ◽  
Dual Inhibitor ◽  
P53 Signaling ◽  
In Silico Studies ◽  
P53 Signaling Pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

scholarly journals Akt Inhibition Enhanced the Growth Inhibition Effects of Low-Dose Heavy-Ion Radiation via the PI3K/Akt/p53 Signaling Pathway in C6 Glioblastoma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Huang ◽  
Wei Zhao ◽  
Xuqiao Wang ◽  
Yingfei Qiu ◽  
Zelin Liu ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Signaling Pathway ◽  
Low Dose ◽  
Ion Irradiation ◽  
Heavy Ion ◽  
C6 Cells ◽  
Carbon Ion ◽  
P53 Signaling ◽  
Heavy Ion Radiation ◽  
P53 Signaling Pathway

BackgroundGlioma has one of the highest mortality rates of all tumors of the nervous system and commonly used treatments almost always fail to achieve tumor control. Low-dose carbon-ion radiation can effectively target cancer and tumor cells, but the mechanisms of growth inhibition induced by heavy-ion radiation via the PI3K/Akt signaling pathway are unknown, and inhibition by heavy-ion radiation is minor in C6 cells.MethodsCarbon-ion radiation was used to investigate the effects of heavy-ion radiation on C6 cells, and suppression of Akt was performed using perifosine. MTT assays were used to investigate optimal perifosine treatment concentrations. Clone formation assays were used to investigate the growth inhibition effects of carbon-ion radiation and the effects of radiation with Akt inhibition. Lactate dehydrogenase release, superoxide dismutase activity, and malondialdehyde content were assessed to investigate oxidative stress levels. Expression levels of proteins in the PI3K/Akt/p53 signaling pathway were assessed via western blotting.ResultsThe 10% maximum inhibitory concentration of perifosine was 19.95 μM. In clone formation assays there was no significant inhibition of cell growth after treatment with heavy-ion irradiation, whereas perifosine enhanced inhibition. Heavy-ion radiation induced lactate dehydrogenase release, increased the level of malondialdehyde, and reduced superoxide dismutase activity. Akt inhibition promoted these processes. Heavy-ion radiation treatment downregulated Akt expression, and upregulated B-cell lymphoma-2 (Bcl-2) expression. p53 and Bcl-2 expression were significantly upregulated, and Bcl-2-associated X protein (Bax) expression was downregulated. The expression profiles of pAkt, Bcl-2, and Bax were reversed by perifosine treatment. Caspase 3 expression was upregulated in all radiation groups.ConclusionsThe growth inhibition effects of low-dose heavy-ion irradiation were not substantial in C6 cells, and Akt inhibition induced by perifosine enhanced the growth inhibition effects via proliferation inhibition, apoptosis, and oxidative stress. Akt inhibition enhanced the effects of heavy-ion radiation, and the PI3K/Akt/p53 signaling pathway may be a critical component involved in the process.

scholarly journals Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1236
Author(s):  
Dorota Gudanis ◽  
Karolina Zielińska ◽  
Daniel Baranowski ◽  
Ryszard Kierzek ◽  
Piotr Kozłowski ◽  
...  
Keyword(s):  
Target Sequence ◽  
Rich Region ◽  
Rna Sequences ◽  
Single Nucleotide ◽  
Alternative Structures ◽  
Single Nucleotide Change ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Target Rna ◽  
Insight Into

In this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ or 5′–GGGCGGG–3′ fragments. Using biophysical methods, we studied the effect of oligonucleotide types (DNA, RNA), non-nucleotide modifications (aliphatic linkers or abasic), and covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif. We demonstrated that all examined non-nucleotide modifications could mimic the external loops in the G-quadruplex domain of QDH structures without affecting their stability. Additionally, some modifications, in particular the presence of two abasic residues in the G-rich oligonucleotide, can induce the formation of non-canonical QDH instead of the Dss structure upon hybridization to a target sequence containing the GGGCUGG motif. Our results offer new insight into the sequential requirements for the formation of G-quadruplexes and provide important data on the effects of non-nucleotide modifications on G-quadruplex formation.

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