Qu Zhi, Deng Lugang, Feng Chunqian, Guo Peisen, Wang Peixi, Liu Nan
Institute of Environment and Health, South China Hospital of Shenzhen University, Shenzhen 518116, China.
School of Nursing and Health, Henan University, Kaifeng 475004, China.
Curr Res Toxicol. 2024 Aug 24;7:100192. doi: 10.1016/j.crtox.2024.100192. eCollection 2024.
At present, hundreds of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been confirmed to be related to the toxicity of cadmium (Cd). However, the role of circular RNAs (circRNAs) in the toxicity of Cd and the underlying regulatory mechanisms remain unclear. In this study, we chose human normal liver cells (L-02) as a model to investigate changes in transcriptome expression levels following exposure to Cd. Total RNA of each sample was extracted by Trizol method, and the expression profiles of circRNAs, miRNAs and mRNAs of each sample were determined by microarray hybridization and scanning. After standardizing the data, differential circRNAs, miRNAs, and mRNAs associated with the toxic effects of Cd were identified. By screening the predicted circRNAs, miRNAs, and mRNAs, we constructed a competing endogenous RNA (ceRNA) network, and predicted the main biological functions and metabolic pathways influenced by Cd toxicity. Our comprehensive screening strategy led to the identification of 266 different circRNAs, 223 different miRNAs and 519 different mRNAs exhibiting differential expression. Following further screening, even circRNAs, 10 miRNAs and 97 mRNAs were incorporated into the ceRNA network. After performing GO enrichment and KEGG pathway analyses on the 97 mRNAs within the ceRNA network, which indicated that the circRNAs in the ceRNA network are poised to modulate key cellular processes, including cell proliferation, apoptosis, oxidative stress and inflammatory responses under the toxic effects of Cd-induced damage in L-02 cells.
目前，已有数百种长链非编码RNA（lncRNAs）和微小RNA（miRNAs）被证实与镉（Cd）的毒性有关。然而，环状RNA（circRNAs）在Cd毒性中的作用及其潜在调控机制仍不清楚。在本研究中，我们选择人正常肝细胞（L-02）作为模型，研究暴露于Cd后转录组表达水平的变化。采用Trizol法提取每个样本的总RNA，并通过微阵列杂交和扫描确定每个样本的circRNAs、miRNAs和mRNAs的表达谱。在对数据进行标准化处理后，鉴定出与Cd毒性作用相关的差异circRNAs、miRNAs和mRNAs。通过筛选预测的circRNAs、miRNAs和mRNAs，我们构建了一个竞争性内源性RNA（ceRNA）网络，并预测了受Cd毒性影响的主要生物学功能和代谢途径。我们的综合筛选策略鉴定出266种不同的circRNAs、223种不同的miRNAs和519种不同的mRNAs呈现差异表达。进一步筛选后，有8种circRNAs、10种miRNAs和97种mRNAs被纳入ceRNA网络。对ceRNA网络中的97种mRNAs进行GO富集分析和KEGG通路分析，结果表明ceRNA网络中的circRNAs可能在Cd诱导的L-02细胞毒性损伤下调节关键细胞过程，包括细胞增殖、凋亡、氧化应激和炎症反应。
