Correlation of autophagy-related genes for predicting clinical prognosis in colorectal cancer

2021 ◽  
Author(s):  
Liyan Liu ◽  
Jilin Zhang ◽  
Hongdong Liu ◽  
Min Shi ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Stage Iii ◽  
Platinum Drug ◽  
P53 Signaling ◽  
Kaplan Meier ◽  
Erbb Signaling ◽  
Inhibitor Resistance ◽  
P53 Signaling Pathway ◽  
Erbb Signaling Pathway

Aim: Autophagy plays a controversial role in cancer. The role of autophagy-related genes (ARGs) in colorectal cancer (CRC) was evaluated based on publicly available data from The Cancer Genome Atlas and the Human Autophagy Database. Materials & methods: After collecting CRC-related transcript and clinical data and a list of ARGs from public databases, the Wilcoxon test was used to identify the differentially expressed ARGs between CRC and paired normal tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to identify the major biological properties and pathways associated with these genes. Univariate Cox regression was used to identify the prognosis-associated ARGs, and a forest plot was used to visualize the results. Kaplan–Meier analysis of the 5-year survival rate was performed. Univariate and multivariate Cox analyses were used to verify the impact of the prognosis-associated ARGs. Results: A total of 36 differentially expressed genes (16 upregulated and 20 downregulated in CRC) were obtained from among 206 ARGs. There were 53 enriched pathways, including the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway (p- and q-values <0.05). Kaplan–Meier analysis showed that the 5-year survival rate was 46.0% (95% CI: 0.335–0.631) and 76.0% (95% CI: 0.651–0.886) in the high- and low-risk groups, respectively. The high-risk patients had worse survival probability (p = 6.256 × 10-5). Independent-samples t-tests revealed that MAP1LC3C expression was higher in patients aged ≤65 than >65 (p = 0.022); RAB7A expression was higher in patients aged ≤65 than >65 (p = 7.31 × 10-4), higher in M1 than M0 (p = 0.042), higher in N1–3 than N0 (p = 0.002) and higher in stage III and IV than I and II (p = 0.042); risk score was higher in N1–3 than N0 (p = 0.001) and in stage III and IV than I and II (p = 0.002); and WIPI2 expression was higher in M1 than M0 (p = 0.002), higher in N1–3 than N0 (p = 2.059 × 10-7) and higher in stage III and IV than I and II (p = 2.299 × 10-7). There were no differences in risk score between males and females (p = 0.593), T1–2 and T3–4 (p = 0.082) or M0 and M1 (p = 0.072). Univariate and multivariate Cox analyses showed that RAB7A was a lower-risk gene, while MAP1LC3C, WIPI2, DAPK1, ULK3 and PELP1 were high-risk genes. Conclusion: Certain ARGs are potential prognostic molecular markers of poor prognosis in CRC. Additionally, the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway may be critical pathways regulated by ARGs in CRC.

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 Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium Via p53 Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7002
Author(s):  
Longlin Zhang ◽  
Mengmeng Ma ◽  
Zhengyi Li ◽  
Haihan Zhang ◽  
Xi He ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signaling Pathway ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Nucleotide Metabolism ◽  
Normal Operation ◽  
Protective Effects ◽  
P53 Signaling ◽  
P53 Signaling Pathway

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders.

p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53 R337H mutation carriers

2017 ◽  
Vol 17 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Gabriel S. Macedo ◽  
Igor Araujo Vieira ◽  
Fernanda Salles Luiz Vianna ◽  
Barbara Alemar ◽  
Juliana Giacomazzi ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
Mutation Carriers ◽  
Tumor Phenotype ◽  
P53 Signaling Pathway

scholarly journals N-α-Acetyltransferase 10 protein inhibits invasion and metastasis of oral squamous cell carcinoma via regulating Pirh2-p53 signaling pathway

2020 ◽  
Author(s):  
Fazhan Wang ◽  
Jun Zheng ◽  
Yongyong Yang ◽  
Jie Yang ◽  
Ting Luo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Nude Mice ◽  
Invasion And Metastasis ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background Naa10p (N-α-Acetyltransferase 10 protein) was reported to be involved in tumor invasion and metastasis in several of tumors. However, the role and mechanism of Naa10p mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Methods The functional role of Naa10p in OSCC cells were determined using Transwell assay in vitro and xenograft tumorigenesis in nude mice. Immunoprecipitation, GST-pull down assays and immunofluorescence were performed to confirm the interaction between Naa10p and RelA/p65 in OSCC cells. Lastly, luciferase reporter assays, chromatin immunoprecipitation (ChIP) and western blot were used to evalute the effect of Naa10p expression on the Pirh2-p53 signaling pathway. Results Naa10p inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, there is a physical interaction between Naa10p and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, MMP-2 and MMP-9. Conclusion Naa10p function as a tumor metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis, and might be a prognostic marker as well as a therapeutic target for OSCC.

Sign in / Sign up

Export Citation Format

Share Document