MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer.
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.
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Zhaojing
Z
Jiang
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Qiancheng
Q
Song
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Rong
R
Zeng
Department of Oncology, Xuzhou Cancer Hospital, Xuzhou, China.
Jing
J
Li
Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jingyu
J
Li
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Xiaochun
X
Lin
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Xing
X
Chen
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jiren
J
Zhang
Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Yanfang
Y
Zheng
D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology
C408631:DCUN1D1 protein, human; C068651:E6 protein, Human papillomavirus type 16; D047908:Intracellular Signaling Peptides and Proteins; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C523369:SFMBT1 protein, human
DCUN1D1; EMT; SFMBT1; cervical cancer; miR-218