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Article Abstract
Unlabelled: N -Methyladenosine (m A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m 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 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 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 A modification in tumor progression. (Hepatology 2017;65:529-543).
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