MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer.
MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer.
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MicroRNA-218 通过靶向 SFMBT1 和 DCUN1D1 抑制宫颈癌中的 EMT、迁移和侵袭
DOI：
10.18632/oncotarget.9850
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Zheng Y
中科院分区：
文献类型：
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作者：
Jiang Z;Song Q;Zeng R;Li J;Li J;Lin X;Chen X;Zhang J;Zheng Y
高危型HPV的反复感染是导致宫颈癌发生和转移的重要原因，但其转移机制至今尚未完全阐明。在这里，我们报道了miR-218（microRNA-218）在宫颈癌组织中下调，特别是在转移癌组织中。我们发现miR-218的表达与宫颈癌患者的临床病理特征相关。miR-218过表达抑制宫颈癌细胞的上皮-间质转化（EMT）、迁移和体外侵袭。此外，miR-218通过直接与mRNA的3′ UTR结合，抑制SFMFBT 1（Scm-like with four MBT domains 1）和DCUN 1D 1（deficient in cullin neddylation 1，domain containing 1）的表达。SFMBT 1的过表达可诱导宫颈癌细胞发生EMT，并增强其迁移和侵袭能力; DCUN 1D 1的过表达可增强宫颈癌细胞的迁移和侵袭能力，但不诱导EMT。宫颈癌组织中miR-218和DCUN 1D 1蛋白的表达呈负相关。重要的是，HPV 16 E6下调了宫颈癌中miR-218的表达，而miR-218挽救了HPV 16 E6对SFMBT 1和DCUN 1D 1表达的促进作用。综上所述，我们的研究结果表明，HPV 16 E6通过抑制miR-218促进宫颈癌的EMT和侵袭，而miR-218通过靶向SFMBT 1和DCUN 1D 1抑制宫颈癌的EMT和侵袭。
Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3′UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.