Cao Fei, Wang Xintong, Ye Qingqing, Yan Fang, Lu Weicheng, Xie Jingdun, Bi Bingtian, Wang Xudong
Department of Anesthesiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Department of Clinical Trial Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Curr Issues Mol Biol. 2023 Aug 16;45(8):6804-6822. doi: 10.3390/cimb45080430.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA-miRNA-mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. , , , , and were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.
化疗诱导的周围神经病变（CIPN）是一线化疗药物常见且严重的副作用。环状RNA（circRNA）与CIPN之间的关联尚不清楚。在本研究中，用紫杉醇构建CIPN模型，同时利用RNA测序鉴定出134个差异表达的circRNA、353个差异表达的长链非编码RNA和86个差异表达的信使RNA（mRNA）。使用miRanda预测circRNA靶向的微小RNA（miRNA），使用TargetScan和miRDB预测miRNA靶向的mRNA。选取测序结果与mRNA预测结果的交集构建circRNA-miRNA-mRNA网络，该网络包括15个circRNA、18个miRNA和11个mRNA。功能富集通路分析和免疫浸润分析显示，差异表达的mRNA在免疫系统中富集，尤其是在T细胞、单核细胞和巨噬细胞中。 、 、 、 和 进一步被鉴定为枢纽基因，并通过RT-qPCR验证，它们与CIPN中的巨噬细胞、浆细胞样树突状细胞和中枢记忆CD4 T细胞相关。此外，我们分别使用DisGeNET、TRRUST和DGIdb数据库预测了枢纽基因的相关疾病、36个潜在转录因子（TF）和30种推定药物。我们的结果表明circRNA和免疫微环境在CIPN中起关键作用，为进一步研究提供了新的见解。
