title: MiR-199a-5p and let-7c cooperatively inhibit migration and invasion by targeting MAP4K3 in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) has a high recurrence rate, and patients exhibit poor survival mainly because intrahepatic metastasis is common. We previously reported that let-7c down-regulation is significantly associated with poor differentiation level in HCC. In the present study, we demonstrate that miR-199a-5p and let-7c are frequently down-regulated in HCC cells and tissues, and low expression of miR-199a-5p is correlated with tumor size, liver envelope invasion. Furthermore, miR-199a-5p and let-7c cooperatively inhibit HCC cell migration and invasion in vitro. MAP4K3 is identified as the direct target of miR-199a-5p and let-7c and this regulation is further confirmed by luciferase reporter assays and Western blotting. In addition, MAP4K3 functions as a metastasis promoter since the results demonstrate that MAP4K3 could promote HCC cell migration and invasion. We also find that miR-199a-5p and let-7c increase the sensitivity of HCC cells to sorafenib.
  
  
  CONCLUSIONS
  We report that miR-199a-5p and let-7c cooperatively and efficiently inhibit HCC cell migration and invasion by targeting the metastasis promoter MAP4K3 and MAP4K3-mediated drug sensitization, suggesting that the use of miRNAs and sorafenib in combination therapy may be a powerful approach to the treatment of HCC.
authors.affiliation: Department of Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Fuwei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Tong
authors.affiliation: Department of Respiratory, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077157:Sorafenib
chemical_list: D035683:MicroRNAs; D010671:Phenylurea Compounds; C531408:mirn199 microRNA, human; C487931:mirnlet7 microRNA, human; D009536:Niacinamide; D000077157:Sorafenib; C543044:MAP4K3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: MAP4K3; hepatocellular carcinoma; let-7c; metastasis; miR-199a-5p