scholarly journals Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

2017 ◽  
Vol 42 (3) ◽  
pp. 1177-1191 ◽  
Author(s):  
Yu Zhang ◽  
Chenyang Zhu ◽  
Bangyao Sun ◽  
Jiawei Lv ◽  
Zhonghua Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
A549 Cell ◽  
Cell Apoptosis ◽  
Integrated Analysis ◽  
Dependent Manner ◽  
Cell Lung Carcinoma ◽  
Synthetic Lethal ◽  
Genome Wide ◽  
Genome Wide Gene Expression

Background/Aims: p53 dysfunction is frequently observed in lung cancer. Although restoring the tumour suppressor function of p53 is recently approved as a putative strategy for combating cancers, the lack of understanding of the molecular mechanism underlying p53-mediated lung cancer suppression has limited the application of p53-based therapies in lung cancer. Methods and Results: Using RNA sequencing, we determined the transcriptional profile of human non-small cell lung carcinoma A549 cells after treatment with two p53-activating chemical compounds, nutlin and RITA, which could induce A549 cell cycle arrest and apoptosis, respectively. Bioinformatics analysis of genome-wide gene expression data showed that distinct transcription profiles were induced by nutlin and RITA and 66 pathways were differentially regulated by these two compounds. However, only two of these pathways, 'Adherens junction' and 'Axon guidance', were found to be synthetic lethal with p53 re-activation, as determined via integrated analysis of genome-wide gene expression profile and short hairpin RNA (shRNA) screening. Further functional protein association analysis of significantly regulated genes associated with these two synthetic lethal pathways indicated that GSK3 played a key role in p53-mediated A549 cell apoptosis, and then gene function study was performed, which revealed that GSK3 inhibition promoted p53-mediated A549 cell apoptosis in a p53 post-translational activity-dependent manner. Conclusion: Our findings provide us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer.

Study on the antitumor activity and mechanism of novel targeted nanodrugs based on miRNA in cervical cancer

2020 ◽  
Vol 10 (8) ◽  
pp. 1218-1223
Author(s):  
Xinping Chen ◽  
Zhichao Ma ◽  
Juan Zhu ◽  
Weihua Xu ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Antitumor Activity ◽  
A549 Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
A549 Cells ◽  
Dependent Manner ◽  
Double Staining ◽  
Dose Dependent

The aim of this study was to investigate the effect of different concentrations of novel targeted nanodrugs based on miRNA on the antitumor activity and mechanism in cervical carcinoma A549 cells. The MTT method was used to determine the effect of different concentrations of novel targeted nanodrugs based on miRNA on A549 cell proliferation, and annexin V FITC/PI double staining flow cytometry was performed to analyze the effect of these nanodrugs on A549 cell apoptosis. Western blotting was performed to observe the effect of these nanodrugs on the expression of Bax, Bcl-2, and caspase-3-related genes involved in A549 cell apoptosis. Compared with the control group, the novel targeted nanodrugs based on miRNA significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner. Results of double staining flow cytometry demonstrated that these nanodrugs could increase the apoptotic rate of A549 cells in a dose-dependent manner 48 h later. Western blotting revealed that these nanodrugs could upregulate the expression of Bax and caspase3 genes and downregulate the expression of Bcl-2 gene. Nanodrugs display an obvious antitumor activity in vitro, and the underlying mechanism may be associated with the upregulation of Bax and caspase-3 gene expression and the downregulation of Bcl-2 gene expression.

scholarly journals Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0169098 ◽  
Author(s):  
Yanliang Zhang ◽  
Qiuyue Xue ◽  
Guoqing Pan ◽  
Qing H. Meng ◽  
Xiaoyu Tuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Copy Number ◽  
Integrated Analysis ◽  
Copy Number Alterations ◽  
Genome Wide

scholarly journals Identifying PIF1 as a Potential Target of Wenxia Changfu Formula in Promoting Lung Cancer Cell Apoptosis: Bioinformatics Analysis and Biological Evidence

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiangjun Yin ◽  
Dongfang Kan ◽  
Jiazhao Ruan ◽  
Delong Wang ◽  
Yi Chai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
A549 Cell ◽  
Cell Apoptosis ◽  
High Efficiency ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Cancer Cell

Lung cancer remains the leading cause of cancer-related deaths worldwide. Traditional Chinese medicine (TCM) is a valuable resource of active natural products and plays an important role in cancer treatment with the advantages of high efficiency and safety. Wenxia Changfu formula (WCF) is modified from Dahuang Fuzi decoction from Han Dynasty and has been used for treating lung cancer in China. Our previous research showed that WCF had an antitumor effect in vivo and in vitro, while the mechanism has not been well illustrated. In this study, the effect of WCF on the proliferative ability in three lung cancer cells and one noncancerous human cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. WCF suppressed A549, H460, and PC-9 cell viability in a dose-dependent manner, with no inhibition of noncancerous MRC-5 cells after 48 h treatment with WCF (0–50 mg/mL). Furthermore, we screened for genes in A549 cells using four WCF-treated samples and four control samples on a gene expression profile microarray. 21 genes were significantly downregulated by WCF, which may potentially play an important role in the proliferation of A549 cells. High-content screening evaluated whether silencing the 21 genes affected A549 cell growth. The results showed that PIF1 knockdown exhibited the most potent inhibition of cell proliferation compared with the other genes. Downregulation of PIF1 increased A549 cell apoptosis and the activity of caspase 3/7. Besides, RT-PCR showed that the expression levels of PIF1 mRNA decreased significantly in A549, H460, and PC-9 cells after WCF treatment. In conclusion, the present observations indicate that WCF may inhibit lung cancer cell proliferation by promoting apoptosis via regulating the expression of PIF1.

scholarly journals Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Mehta ◽  
Karen Grewen ◽  
Brenda Pearson ◽  
Shivangi Wani ◽  
Leanne Wallace ◽  
...  
Keyword(s):  
Gene Expression ◽  
Depressive Symptoms ◽  
Postpartum Depression ◽  
Expression Profiles ◽  
Depression Scale ◽  
Well Being ◽  
Health Concern ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Gene Expression

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

Sign in / Sign up

Export Citation Format

Share Document