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微小RNA-150-3p增强了CGP57380的抗肿瘤作用,并与非小细胞肺癌的良好预后相关。

MicroRNA-150-3p enhances the antitumour effects of CGP57380 and is associated with a favourable prognosis in non-small cell lung cancer.

作者信息

Zheng Hongmei, Fan Songqing, Luo Jiadi, Wen Qiuyuan, Zang Hongjing

机构信息

Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Sci Rep. 2025 Jan 15;15(1):1973. doi: 10.1038/s41598-025-85793-7.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcfc/11733271/7b3ea02a4345/41598_2025_85793_Fig1_HTML.jpg

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