Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China.
Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China; Laboratory of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Int Immunopharmacol. 2023 Sep;122:110606. doi: 10.1016/j.intimp.2023.110606. Epub 2023 Jul 7.
Radiation-induced esophageal injury (RIEI) is an adverse reaction of radiation therapy in patients with esophageal cancer, lung cancer and other malignant tumors. Competitive endogenous RNA (ceRNA) network is known to play a significant role in the onset and progression of many diseases, but the exact mechanism of ceRNA in RIEI has not been fully elucidated. In this study, rat esophaguses were obtained after conducting irradiation under different doses (0 Gy, 25 Gy, 35 Gy). Total RNA was extracted and mRNA, lncRNA, circRNA, and miRNA sequencing was performed. Multiple dose-dependent differentially expressed RNAs (dd-DERs), including 870 lncRNAs, 82 miRNAs, 2478 mRNAs, were obtained through the integration of differential expression analysis and dose-dependent screening (35 Gy ≥ 25 Gy > 0 Gy, or 35 Gy ≤ 25 Gy < 0 Gy). Co-expression analysis and prediction of the binding site in dd-DER were conducted and 27 lncRNAs, 20 miRNAs, and 168 mRNAs were selected to construct a ceRNA network. As the immune microenvironment is crucial for RIEI progression, we constructed an immune-related ceRNA network consisting of 11 lncRNAs, 9 miRNAs, and 9 mRNAs. The expression levels of these immune-related RNAs were verified by RT-qPCR. Immune infiltration analysis showed that the RNAs in the immune-related ceRNA network were mainly associated with the proportion of monocytes, M2 macrophages, activated NK cells, and activated CD4 memory T cells. Drug sensitivity analysis was conducted based on the expression levels of mRNAs in the immune-related ceRNA network, and small molecule drugs with preventive and therapeutic effects on RIEI were identified. In summary, an immune-related ceRNA network associated with RIEI progression was constructed in this study. The findings provide useful information on new potential targets for the prevention and treatment of RIEI.
放射性食管损伤（RIEI）是食管癌、肺癌等恶性肿瘤患者放射治疗的不良反应。竞争性内源性 RNA（ceRNA）网络已知在许多疾病的发生和发展中发挥重要作用，但 ceRNA 在 RIEI 中的确切机制尚未完全阐明。在这项研究中，在不同剂量（0 Gy、25 Gy、35 Gy）下对大鼠食管进行照射后获得总 RNA，并进行 mRNA、lncRNA、circRNA 和 miRNA 测序。通过差异表达分析和剂量依赖性筛选的整合，获得了多个剂量依赖性差异表达 RNA（dd-DER），包括 870 个 lncRNA、82 个 miRNA、2478 个 mRNA（35 Gy≥25 Gy>0 Gy 或 35 Gy≤25 Gy<0 Gy）。对 dd-DER 进行共表达分析和结合位点预测，并选择 27 个 lncRNA、20 个 miRNA 和 168 个 mRNA 构建 ceRNA 网络。由于免疫微环境对 RIEI 进展至关重要，我们构建了一个由 11 个 lncRNA、9 个 miRNA 和 9 个 mRNA 组成的免疫相关 ceRNA 网络。通过 RT-qPCR 验证这些免疫相关 RNA 的表达水平。免疫浸润分析表明，免疫相关 ceRNA 网络中的 RNA 主要与单核细胞、M2 巨噬细胞、活化 NK 细胞和活化 CD4 记忆 T 细胞的比例相关。基于免疫相关 ceRNA 网络中 mRNA 的表达水平进行药物敏感性分析，鉴定出对 RIEI 具有预防和治疗作用的小分子药物。总之，本研究构建了一个与 RIEI 进展相关的免疫相关 ceRNA 网络。研究结果为 RIEI 的预防和治疗提供了新的潜在靶点信息。
