METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N⁶‐methyladenosine‐dependent primary MicroRNA processing

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• 作者：Jin‐zhao Ma ; Fu Yang ; Chuan‐chuan Zhou ; Feng Liu ; Ji‐hang Yuan ; Fang Wang ; Tian‐tian Wang ; Qing‐guo Xu ; Wei‐ping Zhou ; Shu‐han Sun
• 刊名：Hepatology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：65
• 期：2
• 页码：529-543
• 全文大小：1.1MB
• ISSN：1527-3350

文摘

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. Conclusion: 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).