Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S‐phase transition

Ghule, Prachi N.; Seward, David J.; Fritz, Andrew J.; Boyd, Joseph R.; Wijnen, André J. van; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.

doi:10.1002/jcp.26741

Cited by 13 publications

(7 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell cycle consists of S, M, G1, and G2 phases, and ordered cell cycle regulates the proliferation of eukaryotic cells 9. Among them, G1/S transition is quite important for its role in initiation and completion of DNA replication 10. Being in the same conditions, cells with decreased percentage of G1 phase indicate a relatively high level of proliferation ability 11.…”

Section: Discussionmentioning

confidence: 99%

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

Wei

Cao

et al. 2019

OTT

View full text Add to dashboard Cite

BackgroundNuclear auto-antigenic sperm protein (NASP) has been implicated in tumorigenesis. However, its role in melanoma is still unclear.Materials and methodsIn the present study, we detected the mRNA and protein level of NASP in melanoma cell lines and tissues. Then the role of NASP was investigated by transfecting with NASP siRNAs. Finally, the prognosis of NASP was analyzed in 100 melanoma patients through Cox regression and Kaplan–Meier analyses.ResultsWe showed that NASP was significantly overexpressed in melanoma tissues, and unregulated NASP promoted melanoma cell proliferation via promoting cell cycle G1/S phase transition. Additionally, the expression of NASP was closely related to proliferating cell nuclear antigen, a widely accepted biomarker for cell proliferation. Clinically, we found that a high level of NASP predicated poor overall survival and high cumulative recurrence rates. Multivariate analysis revealed that NASP was a risk biomarker for predicting the prognosis of melanoma patients.ConclusionElevated NASP plays an important role in melanoma cell proliferation and tumor progression, and it can be used as an independent prognostic biomarker for melanoma patients.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

Wei

Cao

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…Behind the complex 3-D structural organization of the cell nucleus is a striking degree of functional order ( Figure 1B) wherein specific genomic functions such as DNA replication, transcription, and RNA splicing are compartmentalized within discrete sites along with a host of nuclear bodies such as the PML, Cajal, and histone loci. 1,6,8,39,[56][57][58][59][60][61][62][63] While our understanding of the biogenesis and assembly of various nuclear bodies are still in their infancy, insight has been gained from physiochemical considerations. For example, it has been proposed that nuclear bodies form when proteins bind and cross-link the chromatin as polymer segments thereby collapsing the chromatin into globule-like configurations.…”

Section: Interactions Of Ct Within the Nuclear Milieumentioning

confidence: 99%

Chromosome territories and the global regulation of the genome

Fritz

Sehgal

Pliss

et al. 2019

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

Spatial positioning is a fundamental principle governing nuclear processes. Chromatin is organized as a hierarchy from nucleosomes to Mbp chromatin domains (CD) or topologically associating domains (TADs) to higher level compartments culminating in chromosome territories (CT). Microscopic and sequencing techniques have substantiated chromatin organization as a critical factor regulating gene expression. For example, enhancers loop back to interact with their target genes almost exclusively within TADs, distally located coregulated genes reposition into common transcription factories upon activation, and Mbp CDs exhibit dynamic motion and configurational changes in vivo. A longstanding question in the nucleus field is whether an interactive nuclear matrix provides a direct link between structure and function. The findings of nonrandom radial positioning of CT within the nucleus suggest the possibility of preferential interaction patterns among populations of CT. Sequential labeling up to 10 CT followed by application of computer imaging and geometric graph mining algorithms revealed cell‐type specific interchromosomal networks (ICN) of CT that are altered during the cell cycle, differentiation, and cancer progression. It is proposed that the ICN correlate with the global level of genome regulation. These approaches also demonstrated that the large scale 3‐D topology of CT is specific for each CT. The cell‐type specific proximity of certain chromosomal regions in normal cells may explain the propensity of distinct translocations in cancer subtypes. Understanding how genes are dysregulated upon disruption of the normal “wiring” of the nucleus by translocations, deletions, and amplifications that are hallmarks of cancer, should enable more targeted therapeutic strategies.

show abstract

“…During cell cycle regulation, survivin is a key protein that indicates cell cycle progression, and the complex of cyclin D1 and CDK4 directly regulates cell cycle progression[13]. In a previous study, overexpression of this complex has been found to induce cell proliferation, whereas p21 inhibited the effect of the cyclin D1/CDK4 complex[14].…”

Section: Resultsmentioning

confidence: 99%

“…In the detection of cell cycle progression, the G1/S transition is one of the main checkpoints[12]. The main regulatory factors in G1/S progression are cyclin D1 and cyclin-dependent kinase 4 (CDK4), which can form complexes to regulate this progress[13-15]. A CDK inhibitor, p21, can change the function of CDK–cyclin complexes by binding to them and then suppressing cell proliferation[16].…”

Section: Introductionmentioning

confidence: 99%

Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways

Yang

Liu

Shang

et al. 2019

WJGO

View full text Add to dashboard Cite

BACKGROUND Qingjie Fuzheng granules (QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer (CRC). However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs’ anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways. AIM To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8. METHOD First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase (LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21, Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3K/AKT and ERK signaling pathways was examined using the western blot assay to investigate the possible mechanism. RESULTS MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by (6.90% ± 1.03%)–(59.70% ± 1.51%) (HCT-116; P < 0.05) and (5.56% ± 4.52%)–(49.44% ± 2.47%) (HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002 (HCT-116; P < 0.01) and from 0.56 ± 0.054 to 0.81 ± 0.044 (HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells. QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3K, AKT and ERK. CONCLUSION These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3K/AKT and ERK signaling pathways.

show abstract

Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S‐phase transition

Cited by 13 publications

References 74 publications

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

Chromosome territories and the global regulation of the genome

Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways

Contact Info

Product

Resources

About