title: METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6-methyladenosine-dependent primary MicroRNA processing.
abstract: N6-Methyladenosine (m6A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m6A modifications are decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase-like 14 (METTL14) is the main factor involved in aberrant m6A modification. Moreover, METTL14 down-regulation acts as an adverse prognosis factor for recurrence-free survival of hepatocellular carcinoma and is significantly associated with tumor metastasis in vitro and in vivo. We confirm that METTL14 interacts with the microprocessor protein DGCR8 and positively modulates the primary microRNA 126 process in an m6A-dependent manner. Further experiments show that microRNA 126 inhibits the repressing effect of METTL14 in tumor metastasis.
  
  
  
  These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m6A modification in tumor progression. (Hepatology 2017;65:529-543).
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Jin-Zhao
authors: JZ
authors: Ma
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Fu
authors: F
authors: Yang
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Chuan-Chuan
authors: CC
authors: Zhou
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Feng
authors: F
authors: Liu
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Ji-Hang
authors: JH
authors: Yuan
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Fang
authors: F
authors: Wang
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Tian-Tian
authors: TT
authors: Wang
authors: Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Qing-Guo
authors: QG
authors: Xu
authors: Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Wei-Ping
authors: WP
authors: Zhou
authors: Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Shu-Han
authors: SH
authors: Sun
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics; D034622:RNA Interference; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D035683:MicroRNAs; C010223:N-methyladenosine; C587355:METTL14 protein, human; D008780:Methyltransferases; D000241:Adenosine