Dataset Information

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

ABSTRACT: Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 ?mol/L for 24 h. Here, we identified 1,484 differentially expressed genes (DEGs) in our transcript profiling data, with the majority of differentially expressed transcripts being downregulated. Our results also showed that these DEGs were enriched in pathways associated with the cell cycle, including DNA replication, chromatin assembly, and DNA repair. Using the differential expressed genes related to cell cycle, a weighted gene co-expression network was constructed and a key mRNA-lncRNA regulation module was identified under a scale-free network with topological properties. Additionally, key driver analysis (KDA) was applied to the mRNA-lncRNA regulation module to identify the driver genes. The KDA revealed that ARD3 (FDR = 1.46 × 10^-22), SND1 (FDR = 5.24 × 10^-8), and lnc-DHX32-2:1 (FDR = 1.43 × 10^-17) were particularly highlighted in the category of G2/M, G1/S, and M phases. Moreover, several genes we identified exhibited great connectivity in our causal gene network with every key driver gene, including CDK14, POLA1, lnc-NCS1-2:1, and lnc-FOXK1-4:1 (all FDR < 0.05 in those phases). Together, these results obtained using mathematical approaches and bioinformatics algorithmics might provide potential new mechanisms involved in the cytotoxicity induced by Cr.

SUBMITTER: Zheng P

PROVIDER: S-EPMC7838612 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

Zheng Pai P Kang Yulin Y Han Shuo S Feng Huimin H Ha Feizai F Long Changmao C Zhou Di D Hu Guiping G Chen Zhangjian Z Wang Zengmiao Z Wang Tiancheng T Jia Guang G

Frontiers in genetics 20210113

Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 μmol/L for 24 h. Here, we identified 1,484 differentially expressed genes (DEGs) in our transcript profiling data, with the majority of differentially expressed transcripts being downre ...[more]

PMID: 33519900

Similar Datasets

Project description:BackgroundHexavalent chromium [Cr(VI)] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated.Methods/resultsWe established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI) followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated) that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI) transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI) transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated in all Cr(VI) transformed cells, while genes associated with the interaction between cells and their extracellular matrices were down-regulated. Additionally, expression of genes involved in cell proliferation and apoptosis were also changed.ConclusionThis study is the first to report gene expression profiling of Cr(VI) transformed cells. The gene expression changes across individual chromate exposed clones were remarkably similar to each other but differed significantly from the gene expression found in anchorage-independent clones that arose spontaneously. Our analysis identified many novel gene expression changes that may contribute to chromate induced cell transformation, and collectively this type of information will provide a better understanding of the mechanism underlying chromate carcinogenicity.

Dataset Information

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

Publications

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets