MicroRNA-217 functions as a tumour suppressor gene and correlates with cell resistance to cisplatin in lung cancer.
MicroRNA-217 functions as a tumour suppressor gene and correlates with cell resistance to cisplatin in lung cancer.
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DOI：
10.14348/molcells.2014.0121
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Guo J;Feng Z;Huang Z;Wang H;Lu W
MiR-217可以根据细胞类型作为癌基因或肿瘤抑制基因发挥作用。然而，miR-217在肺癌中的功能至今仍不清楚。本研究旨在评价miR-217在肺癌中的功能，探讨其对肺癌细胞对顺铂敏感性的影响。通过实时荧光定量PCR检测100例患者miR-217的表达。研究miR-217过表达对SPC-A-1和A549细胞增殖、凋亡、迁移和侵袭的影响。通过Targetscan在线软件预测miR-217的靶基因，通过双荧光素酶报告基因试验筛选，并通过Western blot验证。最后，检测miR-217上调对A549细胞对顺铂敏感性的影响。miR-217在肺癌组织中的表达明显低于非癌组织（p < 0.001）。过表达miR-217可通过靶向KRAS显著抑制肺癌细胞的增殖、迁移和侵袭，促进肺癌细胞凋亡。miR-217的上调增强了SPC-A-1和A549细胞对顺铂的敏感性。总之，miR-217通过靶向KRAS抑制肺癌的肿瘤发展，并增强细胞对顺铂的敏感性。我们的结果鼓励研究人员使用顺铂联合miR-217治疗肺癌。该方案可能导致低剂量顺铂应用和顺铂副作用减少。
MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.