Zheng Hongmei, Fan Songqing, Luo Jiadi, Wen Qiuyuan, Zang Hongjing
Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China.
Sci Rep. 2025 Jan 15;15(1):1973. doi: 10.1038/s41598-025-85793-7.
MicroRNA (miRNA) dysregulation has been identified in several carcinomas, including non-small cell lung cancer (NSCLC), and is known to play a role in the development and progression of this disease. We initially conducted a miRNA microarray analysis, which revealed that the MNK inhibitor CGP57380 increased the expression of miR-150-3p. A similar analysis was performed using data from The Cancer Genome Atlas (TCGA). Cell proliferation, colony formation and migration assays were validated in A549 and H157 cells treated with miR-150-3p mimics. Quantitative polymerase chain reaction (qPCR) was then used to detect potential target genes. We observed significant downregulation of miR-150-3p in NSCLC samples compared with normal samples (P = 0.035). High miR-150-3p expression was associated with longer overall survival (P = 0.005), as determined via a tissue microarray (TMA). These results were validated in the TCGA and revealed that miR-150-3p was expressed at low levels in NSCLC tissues (P < 0.0001) and that patients with high miR-150-3p expression had a better prognosis (P = 0.042). Moreover, the combination of miR-150-3p and CGP57380 exerted a synergistic inhibitory effect on colony formation, growth, and migration and induced apoptosis in NSCLC cell lines. We investigated the potential targets of miR-150-3p and successfully validated six potential target genes through qPCR analysis. High miR-150-3p expression may enhance the response to immunotherapy, cisplatin and gemcitabine. In summary, this study underscores the promising therapeutic implications of combining miR-150-3p and CGP57380 for NSCLC treatment. Additionally, this study provides valuable insights into the molecular mechanisms underlying the effects of this treatment.
在包括非小细胞肺癌（NSCLC）在内的多种癌症中，均已发现微小RNA（miRNA）失调，且已知其在该疾病的发生和发展中起作用。我们最初进行了miRNA微阵列分析，结果显示丝裂原活化蛋白激酶相互作用激酶（MNK）抑制剂CGP57380可增加miR-150-3p的表达。我们使用来自癌症基因组图谱（TCGA）的数据进行了类似分析。在用miR-150-3p模拟物处理的A549和H157细胞中验证了细胞增殖、集落形成和迁移试验。然后使用定量聚合酶链反应（qPCR）检测潜在的靶基因。与正常样本相比，我们观察到NSCLC样本中miR-150-3p显著下调（P = 0.035）。通过组织微阵列（TMA）确定，miR-150-3p高表达与更长的总生存期相关（P = 0.005）。这些结果在TCGA中得到验证，显示NSCLC组织中miR-150-3p表达水平较低（P < 0.0001），且miR-150-3p高表达的患者预后较好（P = 0.042）。此外，miR-150-3p与CGP57380联合对NSCLC细胞系的集落形成、生长和迁移具有协同抑制作用，并诱导细胞凋亡。我们研究了miR-150-3p的潜在靶标，并通过qPCR分析成功验证了六个潜在靶基因。miR-150-3p高表达可能增强对免疫疗法、顺铂和吉西他滨的反应。总之，本研究强调了联合miR-150-3p和CGP57380治疗NSCLC的潜在治疗意义。此外，本研究为该治疗效果的分子机制提供了有价值的见解。
