Construction of an immune-related lncRNA-miRNA-mRNA regulatory network in radiation-induced esophageal injury in rats
Construction of an immune-related lncRNA-miRNA-mRNA regulatory network in radiation-induced esophageal injury in rats
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DOI：
10.1016/j.intimp.2023.110606
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发表时间：
2023-07-07
影响因子：
5.6
通讯作者：
Tu，Wenling
中科院分区：
文献类型：
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作者：
Wu，Fengping;Zhang，Xiaolin;Tu，Wenling
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）网络在许多疾病的发生和发展中起着重要作用，但其在RIEI中的确切机制尚未完全阐明。本研究采用不同剂量（0戈伊、25戈伊、35戈伊）的放射线照射大鼠食管，观察食管组织学变化。提取总RNA并进行mRNA、lncRNA、circRNA和miRNA测序。通过差异表达分析和剂量依赖筛选（35戈伊≥ 25戈伊> 0戈伊，或35戈伊≤ 25戈伊< 0戈伊）相结合，获得了多个剂量依赖性差异表达RNA（dd-DER），包括870个lncRNA、82个miRNAs、2478个mRNAs。共表达分析和dd-DER结合位点的预测，并选择27个lncRNA，20个miRNAs和168个mRNAs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。免疫浸润分析显示，免疫相关的ceRNA网络中的RNA主要与单核细胞、M2巨噬细胞、活化的NK细胞和活化的CD 4+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，并鉴定对RIEI具有预防和治疗作用的小分子药物。总之，本研究构建了与RIEI进展相关的免疫相关ceRNA网络。这些发现为RIEI的预防和治疗提供了新的潜在靶点。
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.