METTL16 promotes glycolytic metabolism reprogramming and colorectal cancer progression.

BACKGROUND: Glycolysis is the key hallmark of cancer and maintains malignant tumor initiation and progression. The role of N6-methyladenosine (m6A) modification in glycolysis is largely unknown. This study explored the biological function of m6A methyltransferase METTL16 in glycolytic metabolism and revealed a new mechanism for the progression of Colorectal cancer (CRC). METHODS: The expression and prognostic value of METTL16 was evaluated using bioinformatics and immunohistochemistry (IHC) assays. The biological functions of METTL16 in CRC progression was analyzed in vivo and in vitro. Glycolytic metabolism assays were used to verify the biological function of METTL16 and Suppressor of glucose by autophagy (SOGA1). The protein/RNA stability, RNA immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP) and RNA pull-down assays were used to explore the potential molecular mechanisms. RESULTS: SOGA1 is a direct downstream target of METTL16 and involved in METTL16 mediated glycolysis and CRC progression. METTL16 significantly enhances SOGA1 expression and mRNA stability via binding the "reader" protein insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Subsequently, SOGA1 promotes AMP-activated protein kinase (AMPK) complex ubiquitination, inhibits its expression and phosphorylation, thus upregulates pyruvate dehydrogenase kinase 4 (PDK4), a crucial protein controlling glucose metabolism. Moreover, Yin Yang 1 (YY1) can transcriptionally inhibit the expression of METTL16 in CRC cells by directly binding to its promoter. Clinical data showed that METTL16 expression is positively correlated to SOGA1 and PDK4, and is associated with poor prognosis of CRC patients. CONCLUSIONS: Our findings suggest that METTL16/SOGA1/PDK4 axis might be promising therapeutic targets for CRC.

Acute myocardial infarction in a child with myocardial bridge.

BACKGROUND: Myocardial infarction (MI) is rare in children, and Kawasaki disease is now recognized as the main cause for MI. In this report, we present a child with MI caused by myocardial bridge (MB). METHODS: A 7.5-year-old boy was admitted to Weifang People's Hospital on September 16, 2008 for heart disease. By electrocardiogram, coronary CT angiography, emission computed tomography, and other examinations, he was initially diagnosed as having (1) acute inferior myocardial infarction and extensive anterior myocardial infarction; (2) fulminant myocarditis; or (3) coronary myocardial bridge. He was treated with oxygen, thrombolysis, myocardial nutrition, vitamin C (4.0 g per time), dexamethasone (7.5 mg per time), a large dose of gamma globulin, and interferon. RESULTS: Myocardial enzymes, liver function, C-reactive protein, and troponin-I returned to normal at 21 days after treatment. At 29 days, electrocardiogram indicated that II, III, aVF, V4 - V6 leads had abnormal Q wave, and ST-T changed. The patient was discharged. CONCLUSION: Myocardial bridge may be one of the causes of MI in children.