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

Abstract

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 HCC, especially in metastatic HCC, and that METTL14 is the main factor involved in aberrant m⁶A modification. Moreover, METTL14 down-regulation acts as an adverse prognosis factor for recurrence-free survival (RFS) of HCC and is significantly associated with tumour metastasis in vitro and in vivo. We confirm that METTL14 interacts with the microprocessor protein DGCR8 and positively modulates the pri-miR126 process in an m⁶A-dependent manner. Further experiments show that miR-126 inhibits the repressing effect of METTL14 in tumour metastasis. Conclusions: Our studies reveal an important role of METTL14 in tumour metastasis and provide a fresh view on m⁶A modification in tumour progression.