MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets KRAS
MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets KRAS
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MiR-193a-3p 是肺癌中重要的肿瘤抑制因子并直接靶向 KRAS
DOI：
10.1159/000485491
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Ba, Yi
中科院分区：
文献类型：
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作者：
Fan, Qian;Hu, Xiuting;Ba, Yi
背景/目的：微小RNA（miRNAs）已成为非小细胞肺癌（NSCLC）肿瘤发生和进展的主要调节因子。然而，miR-193 a-3 p在NSCLC中的作用仍不清楚。方法：采用定量RT-PCR方法检测NSCLC肿瘤组织中miR-193 a-3 p的表达水平。采用CCK 8、EdU和细胞迁移试验分析miR-193 a-3 p在NSCLC细胞中的生物学功能。荧光素酶报告基因检测用于验证生物信息学预测的miR-193 a-3 p靶基因。Western blotting和RNA/DNA干扰用于评估miR-193 a-3 p和KRAS之间的关联。结果：miR-193 a-3 p在NSCLC肿瘤组织中表达降低。我们研究了miR-193 a-3 p在体内和体外的生物学效应，发现miR-193 a-3 p的强制表达抑制肿瘤形成并抑制细胞增殖和细胞迁移。发现KRAS是miR-193 a-3 p的潜在靶点，双荧光素酶报告基因测定显示miR-193 a-3 p直接结合KRAS mRNA的3 '-非翻译区（3'-UTR）。此外，我们发现，在NSCLC细胞中，改变KRAS的表达与miR-193 a-3 p诱导的结果相反。重要的是，同时过表达miR-193 a-3 p和KRAS可以抵消两者对细胞功能的影响。结论：这些发现强调了miR-193 a-3 p通过调节KRAS表达在NSCLC发病机制中作为肿瘤抑制因子的重要作用。
Background/Aims: MicroRNAs (miRNAs) have emerged as major regulators of tumour development and progression in non-small cell lung cancer (NSCLC). However, the role of miR-193a-3p in NSCLC is still unclear. Methods: Quantitative RT-PCR was used to detect miR-193a-3p expression levels in NSCLC tumour tissues. CCK8, EdU and cell migration assays were performed to analyse the biological functions of miR-193a-3p in NSCLC cells. Luciferase reporter assays were used to validate the bioinformatics-predicted target genes of miR-193a-3p. Western blotting and RNA/DNA interference carried out to evaluate the association between miR-193a-3p and KRAS. Results: miR-193a-3p expression was decreased in the NSCLC tumour tissues. We investigated the biological effects of miR-193a-3p both in vivo and in vitro and found that enforced expression of miR-193a-3p inhibited tumour formation and suppressed cell proliferation and cell migration. KRAS was found to be a potential target of miR-193a-3p, and dual luciferase reporter assays showed that miR-193a-3p directly binds to the 3’-untranslated region (3’-UTR) of KRAS mRNA. In addition, we found that changing the expression of KRAS had the opposite results to those induced by miR-193a-3p in the NSCLC cells. Importantly, simultaneous overexpression of miR-193a-3p and KRAS could counteract the effects of both on cellular functions. Conclusion: These findings highlight an important role for miR-193a-3p as a tumour suppressor in NSCLC pathogenesis via the regulation of KRAS expression.