Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Thoracic & Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Clin Pharmacol Ther. 2018 Jun;103(6):1061-1073. doi: 10.1002/cpt.870. Epub 2017 Oct 16.
This integrative multistage study was aimed to identify circulating microRNAs (miRNAs) as prognostic biomarkers and investigate the treatment target for early-stage non-small cell lung cancer (NSCLC) patients. In stage I-II NSCLC patients, we screened and validated the miRNA ratio signatures predictive of prognosis in serum. In tumor, we found that the expression of miR-150 in identified miRNA signatures was also associated with survival. Increased miR-150 expression promoted NSCLC cell proliferation and migration and vice versa. Specific mRNA cleavage sites targeted by endogenous miR-150 in 3' untranslated region (UTR) of SRCIN1 was identified by utilizing our recently developed novel Stem-Loop-Array reverse-transcription polymerase chain reaction (SLA-RT-PCR) assay. The blocking action of miR-150 resulted in repressed NSCLC cell growth in vitro and knockdown of miR-150 caused substantial tumor volume reduction in vivo. Our findings suggest that miR-150 binding on specific recognition sites in 3' UTR of tumor suppressor gene SRCIN1 present a potential therapeutic target for NSCLC.
本综合多阶段研究旨在鉴定循环 microRNAs (miRNAs) 作为预后生物标志物,并研究早期非小细胞肺癌 (NSCLC) 患者的治疗靶点。在 I 期-II 期 NSCLC 患者中,我们筛选和验证了预测血清预后的 miRNA 比值特征。在肿瘤中,我们发现鉴定 miRNA 特征中的 miR-150 表达也与生存相关。miR-150 表达增加促进 NSCLC 细胞增殖和迁移,反之亦然。通过利用我们最近开发的新型茎环-array 逆转录聚合酶链反应 (SLA-RT-PCR) 检测,鉴定了内源性 miR-150 在 SRCIN1 3'非翻译区 (UTR) 中靶向的特定 mRNA 切割位点。miR-150 的阻断作用导致体外 NSCLC 细胞生长受到抑制,体内 miR-150 敲低导致肿瘤体积显著减少。我们的研究结果表明,miR-150 结合在肿瘤抑制基因 SRCIN1 的 3'UTR 中的特定识别位点上,为 NSCLC 提供了一个潜在的治疗靶点。