Crosstalk between P53 and DNA damage response in ageing

Mohammadzadeh, Amir; Mirza-Aghazadeh-Attari, Mohammad; Hallaj, Shahin; Saei, Amir Ata; Alivand, Mohammad Reza; Valizadeh, Amir; Yousefi, Bahman; Majidinia, Maryam

doi:10.1016/j.dnarep.2019.05.004

Cited by 27 publications

(15 citation statements)

References 124 publications

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“…In this procedure, the balance between tumour-promoting proteins and anti-tumour proteins is disturbed. p53 is a well-known anti-tumour factor that has been considered as "molecular police" to monitor the integrity of genome during DNA replication [10]. Once activated, p53 will bind to DNA and induce the accumulation of p21.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells

Guo

Lan

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Prolyl hydroxylase domain proteins (PHD2) is an oxygen sensor that is able to induce hypoxia-inducible factor-a (HIF-a) degradation under normoxic condition. The present paper designed to reveal the function of PHD2 in hepatocellular carcinoma (HCC) cells proliferation, migration and invasion. Methods: qRT-PCR and Western blot were carried out to see the expression of PHD2 in HCC tissues and cell lines. PHD2 expression in Huh7 and HepG3B cells was overexpressed or suppressed by transfection and then the changes of cell proliferation, migration and invasion were detected by CCK-8 assay, transwell assay and Western blot. Results: PHD2 was highly expressed in HCC tissues and cell lines (Huh7, Hep3B, SK-HEP-1, HCCLM3 and MHCC97) as relative to para-cancerous non-tumour tissues and a normal hepatocyte line MIHA. PHD2 overexpression promoted Huh7 and Hep3B cells viability, migration and invasion. Meanwhile, CyclinD1, c-Myc, MMP-2, MMP-9 and Vimentin were up-regulated, while p53 was down-regulated by PHD2 overexpression. PHD2 silence led to a contrary impact. Further, PHD2 overexpression up-regulated Ras and Raf expression and induced phosphorylation of MEK, ERK, JAK1 and STAT3. Conclusion: PHD2 exhibited pro-tumour functions in HCC cells. PHD2 promoted HCC possibly through Ras/Raf/MEK/ERK and JAK1/STAT3 pathways. HIGHLIGHTS 1. PHD2 is highly expressed in HCC tissue and cell lines; 2. PHD2 promotes the proliferation of Huh7 and HepG3B cells; 3. PHD2 enhances Huh7 and HepG3B cells migration and invasion; 4. PHD2 activates Ras/Raf/MEK/ERK and JAK1/STAT3 signalling.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells

Guo

Lan

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Similarly, we discovered that silencing of circRNA_0005075 could significantly suppress the GC cell growth rate based on the results of CCK-8 and EDU assay. However, the precise mechanism of how circRNA_0005075 regulate GC cell proliferation was poorly understood.In recent year, p53 had gained increasing attention for its tumour inhibitory effect, including cell-cycle arrest, cell death, DNA repair and others 20,21. Previous study demonstrated that the deletion of p53 could promote liver cancer progression via activating mevalonate pathway 22.…”

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confidence: 99%

CircRNA_0005075 suppresses carcinogenesis via regulating miR‐431/p53/epithelial‐mesenchymal transition axis in gastric cancer

Chen

Song

et al. 2020

Cell Biochemistry & Function

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This study was aimed to explore the expression and biological function of circRNA_0005075 in gastric cancer (GC) progression and its underlying mechanism. First, the expression level of circRNA_0005075 and microRNA-431 (miR-431) in GC tissues were detected with the quantitative real-time polymerase chain reaction. In addition, after down-regulated the circRNA_0005075 expression by plasmid transfection in GC cells, the Cell Counting Kit-8 (CCK-8), EDU, transwell assay were conducted to evaluate the function of circRNA_0005075 or miR-431 on cell proliferation, metastasis in vitro. Moreover, p53 and Epithelial-mesenchymal transition (EMT) pathway related proteins were also measured with western blotting. Then, our data revealed that CircRNA_0005075 was found to be significantly up-regulated in GC tissues as well as GC cell lines, and the GC patients with higher CircRNA_0005075 expression were more likely to have poor outcomes. Downregulation of CircRNA_0005075 could significantly suppress the GC cell proliferation and cell metastasis ability, while the addition of miR-431 inhibitors could counteract this effect. Importantly, we discovered that the silencing of circRNA_0005075 could weaken the micro-RNA sponge function for miR-431, and then upregulate the expression of p53 and forbid the EMT signalling pathway, and finally suppress the tumourigenesis of GC. To sum up, CircRNA_0005075 could inhibit cell growth and metastasis of GC through regulating the miR-431/p53/EMT axis. Significance of the study: The research clearly elucidated the potential role and relative regulatory mechanism of circRNA_0005075 in gastric cancer (GC) progression. Briefly, circRNA_0005075 could directly inhibit the expression level of miR-431, then regulate the p53/Epithelial-mesenchymal transition axis, and finally inhibit cell growth and metastasis in GC. Consequently, circRNA_0005075 might act as an oncogene in the GC procession, which provides a promising way for the treatment of GC.

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“…DNA replication during the S-phase may control the survival of post-mitotic cells by DNA repair mechanisms or apoptosis followed by DNA damage, which seems to be the case in neurodegenerative diseases (Tokarz et al, 2016). Furthermore, DNA damage response signaling can be modulated by tumor suppressor p53 and may also contribute to apoptosis in aging and age-related neurodegenerative disorders (Mohammadzadeh et al, 2019). These pathways showed similar expression patterns as those associated with the mitotic cell cycle, and therefore a lower expression of these DNA damage response pathways in caudal regions is related to cortical atrophy in Parkinson's disease.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease

Keo

Dzyubachyk

Hilten

et al. 2020

Preprint

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Cortical atrophy is a common manifestation in Parkinson's disease, particularly in later disease stages. Here, we investigated patterns of cortical thickness using T1-weighted anatomical MRI data of 149 Parkinson's disease patients and 369 controls. To elucidate the molecular underpinnings of cortical thickness changes in Parkinson's disease, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and neuroimaging features. For this purpose, we used partial least squares regression to identify gene expression patterns correlated with cortical thickness changes. In addition, we identified gene expression patterns underlying the relationship between cortical thickness and clinical domains of Parkinson's disease. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in Parkinson's disease are enriched in biological pathways related to sumoylation, regulation of mitotic cell cycle, mitochondrial translation, DNA damage responses, and ER-Golgi traffic. The associated pathways were highly related to each other and all belong to cellular maintenance mechanisms. The expression of genes within most pathways was negatively correlated with cortical thickness changes, showing higher expression in regions associated with decreased cortical thickness (atrophy). On the other hand, sumoylation pathways were positively correlated with cortical thickness changes, showing higher expression in regions with increased cortical thickness (hypertrophy). Our findings suggest that alterations in the balanced interplay of these mechanisms play a role in changes of cortical thickness in Parkinson's disease and possibly influence motor and cognitive functions. Abbreviations: AHBA = Allen Human Brain Atlas; CT = cortical thickness; LED = levodopa equivalent dose; MDS-UPDRS = Movement Disorder Society-sponsored revision of the unified Parkinson's disease rating scale; MMSE = mini-mental state examination; PLS = partial least squares; SENS-PD = severity of non-dopaminergic symptoms in Parkinson's disease Running title: Gene expression and cortical thickness

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Crosstalk between P53 and DNA damage response in ageing

Cited by 27 publications

References 124 publications

RETRACTED ARTICLE: PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells

RETRACTED ARTICLE: PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells

CircRNA_0005075 suppresses carcinogenesis via regulating miR‐431/p53/epithelial‐mesenchymal transition axis in gastric cancer

Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease

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