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血清 microRNA-150 预测早期非小细胞肺癌的预后,并通过靶向肿瘤抑制基因 SRCIN1 促进肿瘤细胞增殖。

Serum MicroRNA-150 Predicts Prognosis for Early-Stage Non-Small Cell Lung Cancer and Promotes Tumor Cell Proliferation by Targeting Tumor Suppressor Gene SRCIN1.

机构信息

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.

出版信息

Clin Pharmacol Ther. 2018 Jun;103(6):1061-1073. doi: 10.1002/cpt.870. Epub 2017 Oct 16.

Abstract

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.

摘要

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。

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