Related Experiment Video
Updated: Mar 13, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6 -methyladenosine-dependent
Jin-Zhao Ma1, Fu Yang1, Chuan-Chuan Zhou1
1Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Abstract:
N6 -Methyladenosine (m6 A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m6 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 m6 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 m6 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 m6 A modification in tumor progression. (Hepatology 2017;65:529-543).
Insights
Methyltransferase-like 14 (METTL14) down-regulation is linked to decreased N6 -Methyladenosine (m6 A) modifications and promotes hepatocellular carcinoma metastasis. METTL14 impacts microRNA 126 processing, affecting tumor progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- N6 -Methyladenosine (m6 A) modifications regulate numerous biological processes.
- The role of m6 A in hepatocellular carcinoma (HCC) progression remains largely unelucidated.
- Aberrant epigenetic modifications are hallmarks of cancer development.
Purpose of the Study:
- To investigate the role of m6 A modification and its associated enzymes in hepatocellular carcinoma.
- To determine the prognostic significance of methyltransferase-like 14 (METTL14) in HCC.
- To elucidate the molecular mechanisms by which METTL14 influences HCC metastasis.
Main Methods:
- Analysis of m6 A modification levels in HCC tissues.
- Quantitative real-time PCR and Western blot to assess METTL14 expression.
- In vitro and in vivo assays to evaluate tumor metastasis.
- Immunoprecipitation assays to study protein interactions.
- MicroRNA processing and functional assays.
Main Results:
- m6 A modifications were significantly decreased in HCC, particularly in metastatic cases.
- METTL14 expression was downregulated in HCC and correlated with poor recurrence-free survival.
- METTL14 down-regulation promoted HCC cell migration and invasion in vitro and metastasis in vivo.
- METTL14 interacts with DGCR8 and positively regulates microRNA 126 processing in an m6 A-dependent manner.
- MicroRNA 126 was found to inhibit METTL14's pro-metastatic effects.
Conclusions:
- METTL14 plays a critical role in suppressing HCC metastasis.
- Downregulation of METTL14 is an adverse prognostic factor for HCC patients.
- METTL14-mediated regulation of microRNA 126 processing is a key mechanism in HCC progression.
- Targeting the m6 A modification pathway, particularly METTL14, may offer novel therapeutic strategies for HCC.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
02:15Experimental RNAi