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A549, human alveolar adenocarcinoma cell, treated with aldehyde

ABSTRACT: To gain deeper insight into the mechanism of toxicity, it is important to identify and characterize mRNAs profiles involved in responses to specific classes of toxicants in conjunction with their impact on gene expression levels. However, few reports have described the effects of toxicants on mRNA expression profiles. Taking into account the prominent role of mRNAs in cancer development, progression, cell cycle control, and proliferation-related processes, it is likely that mRNAs are involved in the toxic response induced by carcinogens. Aldehydes are a well-characterized class of human carcinogens. In the present study, we documented the different expression profiles of mRNAs in environmental carcinogen-exposed A549 cells by mRNA microarray analysis. To evaluate the change in mRNA expression levels, human alveolar cells(A549) were exposed to seven lower-molecular-weight saturated aliphatic aldehyde (LSAAs) for 48h. mRNA expression analysis was conducted using a 4x44k human whole genome oligo microarray (Agilent Technologies, USA).

ORGANISM(S): Homo sapiens

SUBMITTER: Cho Yoon

PROVIDER: S-ECPF-GEOD-56005 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundPaclitaxel is widely used in the treatment of cancer and has a good effect in the treatment of non-small cell lung cancer. The combination of TMT proteomics and bioinformatics is used to systematically analyze the molecular mechanism of paclitaxel in the treatment of lung adenocarcinoma A549 cell, which is helpful to screen new therapeutic targets.MethodsMTT assay was used to analyze the inhibitory effect of paclitaxel on the proliferation of A549 cells. The proteins were identified by TMT quantitative proteomics and the differential expression proteins (DEPs) database was constructed. The DEPs were enriched by Gene Ontology (GO) and KEGG pathway annotation. Based on the information in the STRING database, find the interaction between DEPs, and the protein-protein interaction (PPI) networks of DEPs were constructed and analyzed by using the Cytoscape software. According to the PPI network results, select the hub proteins from DEPs for WB verification.ResultsA total of 5449 proteins were identified in A549 by TMT proteomics. Compared with the control group, 281 DEPs were significantly up-regulated and 218 were significantly down-regulated after paclitaxel treatment. GO functional analysis, we found that the main functions of these DEPs are binding, catalytic activity, molecular function regulator and so on. They are mainly involved in cellular process, metabolic process, biological regulation and so on. KEGG analysis showed that the three most significant signal transduction pathways of DEPs enrichment were DNA replication, steroid biosynthesis, oxidative phosphorylation. In PPI network, there are 294 nodes among which CDK1, MCM2-5 and PCNA are located at the center of proteins interaction. WB analysis confirmed that the expression of CDK1 was significantly down-regulated, consistent with the TMT results.ConclusionPaclitaxel significantly increased the expression of tubulin, binding tubulin to promote A549 cell death. In addition, paclitaxel significantly inhibited the expression of hub proteins, DNA replication and cell cycle pathways, thus killing lung adenocarcinoma cell A549. These findings will enhance the understanding of the mechanism of paclitaxel in the treatment of lung adenocarcinoma cell A549 and provide new valuable targets.

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A549, human alveolar adenocarcinoma cell, treated with aldehyde

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