很多实验证明hsa-miR-126(miR-126)在非小细胞肺癌(NSCLC)细胞系中表达被下调。补回miR-126能通过特定的分子能抑制肿瘤细胞的增殖、迁移、侵袭和存活。本文报道了miR-126参与调控NSCLC细胞对化疗的反应。用miR-126类似物或抑制剂转染A549细胞导致miR-126水平是显著升高、阿霉素和长春新碱的半抑制浓度降低、阿霉素累积增加，血管内皮生长因子A(VEGFA)和多药耐药相关蛋白1(MRP1)均下调，并且Akt信号通路失活。此外，miR-126表达上升抑制了A549异种移植的生长。miR-126通过与VEGFA 3'-非翻译区相互作用有效地下调VEGFA的表达，而补回VEGFA可以部分地削减miR-126对MRP1的抑制。PI3K/Akt信号传导途径的抑制剂LY294002能够消除miR-126的这种效果，这表明miR-126对非小细胞肺癌作用主要是通过对VEGF/PI3K/Akt/MRP1信号传导途径的负调控来实现的。

图例: 小鼠模型中miR-126类似物抑制肿瘤生长

miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A

Xiaolan Zhu, Hao Li, Lulu Long, Lulu Hui, Haining Chen, Xuefeng Wang, Huiling Shen, and Wenlin Xu

The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212001, China.

Increasing evidence suggests that hsa-miR-126 (miR-126) is down-regulated in non-small cell lung cancer (NSCLC) cell lines and the restoration of miR-126 impairs tumor cell proliferation, migration, invasion, and survival by targeting specific molecules. Here, we reported for the first time that miR-126 was involved in regulating the response of NSCLC cells to cancer chemotherapy. After transfected A549 cells with miR-126 mimic or inhibitor, we found that an elevated level of miR-126 was significantly associated with a decreased half maximal inhibitory concentration of adriamycin (ADM) and vincristine, an increased accumulation of ADM, down-regulation of vascular endothelial growth factor A (VEGFA) and multidrug resistance-associated protein 1 (MRP1), and inactivation of the Akt signaling pathway. Furthermore, enhanced expression of miR-126 suppressed the growth of A549 xenograft and inhibited the expression of VEGFA and MRP1. miR-126 could efficiently down-regulate VEGFA expression through the interaction with the VEGFA 3'-untranslated region, whereas restoration of VEGFA could partially attenuate the suppression of MRP1 by miR-126. However, LY294002, an inhibitor of the PI3K/Akt signaling pathway, diminished this effect, suggesting that enhanced expression of miR-126 increased the sensitivity of NSCLC cells to anticancer agents through negative regulation of a VEGF/PI3K/Akt/MRP1 signaling pathway.

全文: http://abbs.oxfordjournals.org/content/44/6/519.full.pdf+html