MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer
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Zhaojing Jiang1,*, Qiancheng Song2,*, Rong Zeng1,*, Jing Li3, Jingyu Li4, Xiaochun Lin1, Xing Chen1, Jiren Zhang1, Yanfang Zheng1
1Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
2Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
3Department of Oncology, Xuzhou Cancer Hospital, Xuzhou, China
4Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
*These authors have contributed equally to this work
Yanfang Zheng, email: firstname.lastname@example.org
Keywords: miR-218, EMT, cervical cancer, SFMBT1, DCUN1D1
Received: December 18, 2015 Accepted: May 20, 2016 Published: June 6, 2016
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.
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