Lei Xiaohong, Qing Ailing, Yuan Xuemei, Qiu Delu, Li Haiyu
Department of Anesthesiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Department of Infectious Disease, Chongqing Public Health Medical Center, Chongqing, China.
DNA Cell Biol. 2020 Nov 17. doi: 10.1089/dna.2020.5531.
Silicosis is the most common type of pneumoconiosis with the fastest progress and the most serious harm. At present, there is still a lack of effective treatment for silicosis, and the molecular mechanism of silicosis is very complex, which is not completely clear. This study aimed to identify crucial long noncoding RNA (lncRNA)-mRNA networks for silica-induced pulmonary fibrosis using microarray data from Gene Expression Omnibus database, including human lung epithelial cells Beas-2B and continuously exposed to 5 μg/mL amorphous silica nanoparticles for 40 passages. Differently expressed genes were calculated by "DESeq2" R package. Then we selected the differently expressed mRNAs (DEmRNAs) and differently expressed long noncoding RNAs (DElncRNAs) data construct lncRNA-mRNA coexpression network using weighted gene coexpression network analysis (WCGNA). A total of 1140 DEmRNA and 1406 DElncRNAs were identified, including 20 upregulated DEmRNAs, 1120 downregulated DEmRNAs as well as 213 upregulated DElncRNAs and 1193 downregulated DElncRNAs. Furthermore, we demonstrate that lncRNA AK131029 was specifically overexpressed in silicosis. Loss-of-function assay indicated that silencing AK131029 of inhibited cell proliferation in human lung fibroblast cells. In conclusion, this study preliminarily indicates that lncRNA AK131029 may play a role in pulmonary fibrosis.
矽肺是最常见的尘肺病类型，进展最快且危害最严重。目前，矽肺仍缺乏有效的治疗方法，其分子机制非常复杂，尚未完全明确。本研究旨在利用来自基因表达综合数据库的微阵列数据，确定二氧化硅诱导肺纤维化的关键长链非编码RNA（lncRNA）-mRNA网络，该数据库包含人肺上皮细胞Beas-2B，并持续暴露于5μg/mL无定形二氧化硅纳米颗粒40代。通过“DESeq2”R包计算差异表达基因。然后，我们使用加权基因共表达网络分析（WCGNA）选择差异表达的mRNA（DEmRNA）和差异表达的长链非编码RNA（DElncRNA）数据构建lncRNA-mRNA共表达网络。共鉴定出1140个DEmRNA和1406个DElncRNA，包括20个上调的DEmRNA、1120个下调的DEmRNA以及213个上调的DElncRNA和1193个下调的DElncRNA。此外，我们证明lncRNA AK131029在矽肺中特异性过表达。功能丧失试验表明，沉默人肺成纤维细胞中的AK131029可抑制细胞增殖。总之，本研究初步表明lncRNA AK131029可能在肺纤维化中发挥作用。
