南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (05): 578-.

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miR-203通过靶向FABP4抑制肺癌细胞的转移

陈纪超,吴旭   

  • 出版日期:2018-05-20 发布日期:2018-05-20

miR-203 inhibits lung cancer cell metastasis by targeting fatty acid binding protein 4

  • Online:2018-05-20 Published:2018-05-20

摘要: 目的探讨脂肪酸转运蛋白4(FABP4)对肺癌细胞转移能力的影响并研究靶向FABP4 的miRNA。方法通过ELISA 和western blot 检测不同转移能力的肺癌细胞FABP4 表达情况。通过shRNA减少FABP4 表达或慢病毒过表达FABP4,观察 其对肺癌细胞转移能力的影响。通过miRNA数据网站预测靶向FABP4 的miRNA,并用Q-PCR检测其在不同转移能力的肺 癌细胞的表达情况。结果高转移能力的NL9980、H661、95C肺癌细胞中FABP4 的表达较低转移能力的L9981、A549、PC13 显著增加(P<0.05)。降低NL9980 细胞中FABP4 的表达,其转移能力被显著抑制(P<0.05);而过表FABP4 后,A549 转移能 力显著增强(P<0.05)。miR-203、miR-361 和miR-539 在高转移能力的肺癌细胞中表达较低转移的显著减少(P<0.05),并且 miR-203 抑制NL9980 细胞FABP4 表达的作用最强。过表达靶向FABP4 位点突变的FABP4 蛋白,可以显著减少miR-203 对 NL9980 细胞转移能力的抑制(P<0.05)。结论FABP4 可以促进肺癌细胞的转移;而miR-203 可靶向抑制FABP4 表达,进而 抑制肺癌细胞的转移。

Abstract: Objective To explore the role of fatty acid binding protein 4 (FABP4) in regulating lung cancer cell metastasis and identify miRNAs that target FABP4. Methods The expression of FABP4 in lung cancer cells with different metastatic potentials was detected using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effects of FABP4 knockdown or overexpression by shRNA or a recombinant lentivirus, respectively, on lung cancer cells metastasis were assessed. The miRNAs that targeted FABP4 were screened using target prediction algorithms and the results were verified with Q-PCR. Results FABP4 expression was significantly higher in lung cancer cell lines with high metastatic potentials (NL9980, H661, and 95C) than in those with low metastatic potentials (L9981, A549, and PC13) (P<0.05). FABP4 knockdown in NL9980 cells resulted in significantly inhibited metastasis of the cells (P<0.05), while FABP4 overexpression obviously promoted the metastasis of A549 cells (P<0.05). The expressions of miR-203, miR-361 and miR-539 were significantly higher in highly metastatic lung cancer cells than in the cells with low metastatic potentials (P<0.05). In NL9980 cells, FABP4 expression was most obviously suppressed by miR-203 (P<0.05), and target site mutational FABP4 overexpression significantly attenuated the inhibitory effect of miR-203 on NL9980 metastasis (P<0.05). Conclusion FABP4 can promote lung cancer metastasis, and by targeting FABP4 to inhibit its expression, miR-203 can suppress the metastasis of lung cancer cells.