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

Pai Zheng; Yulin Kang; Shuo Han; Huimin Feng; Feizai Ha; Changmao Long; Di Zhou; Guiping Hu; Zhangjian Chen; Zengmiao Wang; Tiancheng Wang; Guang Jia

doi:10.3389/fgene.2020.597803

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

Front Genet. 2021 Jan 13:11:597803. doi: 10.3389/fgene.2020.597803. eCollection 2020.

Authors

Pai Zheng¹, Yulin Kang², Shuo Han¹, Huimin Feng¹, Feizai Ha², Changmao Long¹, Di Zhou¹, Guiping Hu³, Zhangjian Chen¹, Zengmiao Wang^{4

5}, Tiancheng Wang², Guang Jia¹

Affiliations

¹ Department of Occupational and Environmental Health Science, School of Public Health, Peking University, Beijing, China.
² Institute of Environmental Information, Chinese Research Academy of Environmental Sciences, Beijing, China.
³ School of Medical Science and Engineering, Beihang University, Beijing, China.
⁴ State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing, China.
⁵ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, United States.

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 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 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.

Keywords: cell cycle; hexavalent chromium; lncRNA; regulation network; transcriptome.