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.

六价铬[Cr（VI）]是一种众所周知的职业致癌物，但导致DNA损伤和细胞周期改变的机理尚未完全阐明。为了研究Cr（VI）对转录的剂量效应，我们将BEAS-2B细胞暴露于浓度为0.2、0.6和1.8μmol/ L的Cr（VI）中24小时。在这里，我们在转录谱分析数据中鉴定了1,484个差异表达基因（DEG），其中大多数差异表达的转录物均被下调。我们的结果还表明，这些DEG富含与细胞周期相关的途径，包括DNA复制，染色质组装和DNA修复。利用与细胞周期相关的差异表达基因，构建了加权基因共表达网络，并在具有拓扑特性的无标度网络下确定了关键的mRNA-lncRNA调控模块。此外，将关键驱动程序分析（KDA）应用于mRNA-lncRNA调节模块以识别驱动程序基因。KDA显示ARD3（FDR = 1.46×10^–22），SND1（FDR = 5.24×10 ^–8）和lnc-DHX32-2：1（FDR = 1.43×10 ^–17）在G2 / M，G1 / S和M相类别中特别突出。此外，我们确定的几个基因在我们的因果基因网络中与每个关键驱动基因均显示出极大的连通性，包括CDK14，POLA1，lnc-NCS1-2：1和lnc-FOXK1-4：1（在这些阶段中所有FDR <0.05） 。总之，使用数学方法和生物信息学算法学获得的这些结果可能会提供潜在的新机制，参与Cr诱导的细胞毒性。