Lv Jin, An Juan, Zhang Yang-Dong, Li Zhao-Xia, Zhao Guang-Li, Gao Jun, Hu Wen-Wei, Chen Huo-Ming, Li Ai-Min, Jiang Qi-Sheng
Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China.
Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China.
Oncol Lett. 2020 Nov;20(5):236. doi: 10.3892/ol.2020.12099. Epub 2020 Sep 14.
Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191*, in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age- and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191* in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191* in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191* expression in A549 cells and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells and metastasis . In conclusion, miR-130a, miR-25 and miR-191* may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.
血清微小RNA(miRNA)已被认为是肺癌诊断的非侵入性生物标志物。然而,目前尚无用于检测放疗相关非小细胞肺癌(NSCLC)转移的敏感且特异的生物标志物。本研究旨在探讨三种血清miRNA,即miRNA(miR)-130a、miR-25和miR-191在NSCLC诊断中的作用,以及它们在辐射介导的A549细胞转移特性发展中的生物学功能。为此,收集了84例NSCLC患者和42例年龄及性别匹配的健康对照者的血清样本。通过定量PCR分析血清miRNA的差异表达。使用Cox比例回归模型确定miRNA表达与NSCLC患者总生存期之间的显著关联。绘制受试者工作特征曲线以评估诊断准确性。通过用miRNA模拟物和抑制剂转染A549细胞,研究miR-130a、miR-25和miR-191在肺癌细胞中的功能。本研究结果表明,NSCLC患者血清中miR-130a、miR-25和miR-191的表达水平高于健康对照者,且这些升高与高龄(≥60岁)、放疗、组织学类型(鳞状癌)、低生存率和低中位生存时间相关。此外,辐射诱导A549细胞和异种移植小鼠模型中miR-130a、miR-25和miR-191表达上调。辐射还促进了A549细胞的侵袭和转移。总之,miR-130a、miR-25和miR-191*可能是NSCLC患者诊断的潜在生物标志物,并可能在NSCLC的辐射介导转移中发挥致癌作用。