miR-194 suppresses high glucose-induced non-small cell lung cancer cell progression by targeting NFAT5
miR-194 suppresses high glucose-induced non-small cell lung cancer cell progression by targeting NFAT5
复制标题
miR-194通过靶向NFAT5抑制高糖诱导的非小细胞肺癌细胞进展
DOI：
10.1111/1759-7714.13038
复制
发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Yu, Pei
中科院分区：
文献类型：
--
作者：
Meng, Xuying;Li, Zhenjin;Yu, Pei
背景糖尿病（DM）与肺癌风险增加有关;然而，确切的分子基础尚不清楚。方法采用基因芯片技术，发现一组microRNA在高糖和低糖处理的肺癌细胞中表达差异。结果其中miR-194的表达有明显变化，有待进一步分析。miR-194在高糖（HG）培养的非小细胞肺癌（NSCLC）细胞和临床NSCLC伴DM组织中显著下调。miR-194的引入显著抑制HG诱导的肺癌细胞的增殖、迁移和侵袭，表明miR-194可能是HG诱导的NSCLC进展过程中的抑制剂。进一步的分析表明，NFAT 5是miR-194的直接靶基因，这通过miR-194与NFAT 5的3 '非翻译区的直接结合来证明。miR-194可在mRNA和蛋白水平上降低NFAT 5的表达，而NFAT 5的过表达逆转了miR-194介导的肺癌细胞增殖、迁移和侵袭能力的降低。结论本研究为探讨NSCLC的进展机制提供了新的思路。在治疗上，miR-194可作为治疗肺癌合并糖尿病患者的潜在靶点。
Background Diabetes mellitus (DM) is linked to an increased risk of lung cancer; however, the exact molecular basis is unclear. Methods We used a microarray method and found a group of microRNAs differently expressed in lung cancer cells at high or low glucose treatment. Results Among these, miR-194 changed significantly, which indicated further analysis. miR-194 was significantly downregulated in non-small cell lung cancer (NSCLC) cells cultured in high glucose (HG) medium and clinical NSCLC tissues with DM. The introduction of miR-194 significantly suppressed the proliferation, migration, and invasion of lung cancer cells induced by HG, suggesting that miR-194 may be a suppressor during HG-induced NSCLC progression. Further analysis indicated that NFAT5 was a direct target gene of miR-194, evidenced by the direct binding of miR-194 with the 3'untranslated region of NFAT5. MiR-194 could decrease the expression of NFAT5 at both messenger RNA and protein levels, while overexpression of NFAT5 reversed the decreased proliferation, migration, and invasion ability mediated by miR-194 in lung cancer cells. Conclusion Our findings provide new insight into the mechanism of NSCLC progression. Therapeutically, miR-194 may serve as a potential target for the treatment of lung cancer patients with DM.