The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway

Xu, Shun; Wu, Weijia; Huang, Huawen; Huang, Ruxiao; Xie, Luoyijun; Su, Ailing; Liu, Shuang; Ren, Zheng; Yuan, Yuan; Zheng, Heng; Sun, Xiaoyan; Xiong, Xing‐Dong; Liu, Xinguang

doi:10.1111/acel.12918

Cited by 51 publications

(43 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hub gene GTSE1 negatively regulates the p53 activity, hence it controls the downstream effects of p53 signalling pathway mediated cell cycle 53 . The Cyclin B2 (CCNA2) hub gene is directly involved in G2/M transition phase during the cell cycle and delays the cellular senescence and apoptosis by p53 54 . Other upregulated pathways reported in dietary gluten restricted mouse model of CeD are apoptosis and DNA repair in lamina propria and epithelium of the small intestine 47 .…”

Section: Discussionmentioning

confidence: 99%

Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Banaganapalli

Mansour

Mohammed

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Celiac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at the time of disease diagnosis and after two years of the gluten-free diet. A series of advanced systems biology approaches like differential gene expression, protein–protein interactions, gene network-cluster analysis were deployed to annotate the candidate pathways relevant to CeD pathogenesis. The duodenum tissues from CeD patients revealed the differential expression of 106 up- and 193 down-regulated genes. The pathway enrichment of differentially expressed genes (DEGs) highlights the involvement of biological pathways related to loss of cell division regulation (cell cycle, p53 signalling pathway), immune system processes (NOD-like receptor signalling pathway, Th1, and Th2 cell differentiation, IL-17 signalling pathway) and impaired metabolism and absorption (mineral and vitamin absorptions and drug metabolism) in celiac disease. The molecular dysfunctions of these 3 biological events tend to increase the number of intraepithelial lymphocytes (IELs) and villous atrophy of the duodenal mucosa promoting the development of CeD. For the first time, this study highlights the involvement of aberrant cell division, immune system, absorption, and metabolism pathways in CeD pathophysiology and presents potential novel therapeutic opportunities.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Banaganapalli

Mansour

Mohammed

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Studies have shown that GSK3B, which acted as egative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, was closely related to Healthy Aging Index [37]. Silencing of CCNA2, which controled both the G1/S and the G2/M transition phases of the cell cycle, emarkably triggered the cellular aging, while CCNA2 overexpression delayed cellular aging [38]. The expression of PTGS with a particular role in the in ammatory response was up-regulated in diseases related to brain aging [39].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Aging represents the main risk factor for a number of debilitating diseases and contributes to increase in mortality. Previous studies have shown that ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. In this study, we proposed a network pharmacology-based method to identify the therapeutic pathways of EGb for aging.Methods The active components of EGb and targets of sample chemicals were obtained from TCMSP database. Aging-related genes were obtained by retrieving the Human Ageing Genomic Resources database and the JenAge Ageing Factor Database. Then, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was built, which was used to investigate pharmacological mechanisms of EGb for Aging.Results 24 active components, 154 targets of active components of EGb and 308 targets of aging were obtained. Network construction and pathway enrichment were carried out after data integration. The research found that flavonoids (quercetin, luteolin, kaempferol) and beta-sitosterol might be the main active component of EGb. The top eight candidate targets, including PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, ESR1, were chosen as EGb’s main therapeutic targets. The results of pathway enrichment participated in various pathways associated with inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance and regulating cellular biological processes, etc. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol and PTGS2 had better binding capacity with kaempferol and quercetin.Conclusions The main components of EGb might act on multiple targets, such as PTGS2, PPARG, DPP4, GSK3B, etc., to regulate multiple pathways and played an anti- aging role by inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance.

show abstract

“…Intricate miRNA feedback loops can modulate senescence programs. For example, a p53/ miRNA/CCNA2 pathway drives senescence independently of the p53/p21 WAF1/Cip1 axis (Xu et al, 2019). Similarly, p53dependent upregulation of miR-34a/b/c downregulates cell proliferation and survival factors (Hermeking, 2010).…”

Section: Transcriptional Signaturesmentioning

confidence: 99%

Cellular Senescence: Defining a Path Forward

Gorgoulis

Adams

Alimonti

et al. 2019

Cell

1,732

2,074

View full text Add to dashboard Cite

Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo. Cellular Senescence: Walking a Line between Life and Death Cell states link both physiological and stress signals to tissue homeostasis and organismal health. In both cases, the outcomes vary and are determined by the signal characteristics (type, magnitude, and duration), spatiotemporal parameters (where and when), and cellular capacity to respond (Gorgoulis et al., 2018). In the case of potentially damaging stress, damage is reversed and the structural and functional integrity of cells restored. Alternatively, damage can be irreversible, and cells activate death mechanisms mainly to restrict the impact on tissue degeneration. Between these extremes, cells can acquire other states, often associated with survival but also with permanent structural and functional changes. An example is the non-proliferative but viable state, distinct from G0 quiescence and terminal differentiation, termed cellular senescence (Rodier and Campisi, 2011). Formally described in 1961 by Hayflick and colleagues, cellular senescence, derived from the latin word senex meaning ''old'' (Hayflick and Moorhead, 1961), was originally observed in normal diploid cells that

show abstract

The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway

Cited by 51 publications

References 33 publications

Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Cellular Senescence: Defining a Path Forward

Contact Info

Product

Resources

About