METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N 6‐methyladenosine‐dependent primary MicroRNA processing

Abstract

N 6 ‐Methyladenosine (m 6 A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m 6 A modifications are decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase‐like 14 (METTL14) is the main factor involved in aberrant m 6 A 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 m 6 A‐dependent manner. Further experiments show that microRNA 126 inhibits the repressing effect of METTL14 in tumor metastasis. Conclusion : These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m 6 A modification in tumor progression. (H epatology 2017;65:529‐543).