Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Previous epigenetic studies are mainly focused on aberrant DNA methylation and histone modifications. Recently, emerging evidence suggested that besides DNA and histone proteins, mRNA are also subjected to various reversible chemical modifications. N6-methyladenosine (m6A) is the most abundant chemical modification on eukaryotic mRNA and is important to the regulation of mRNA stability, splicing, and translation. However, limited studies have addressed the pathological implications of m6A deregulation in disease models. We found that deregulation of m6A modification may play a crucial role in human carcinogenesis. We discovered that the major RNA m6A methyltransferase METTL3 was frequently up-regulated in liver cancer and multiple solid tumours. We also identified putative tumor suppressor SOCS2 as a novel target of METTL3. m6A modification promoted SOCS2 degradation through m6A reader YTHDF2 dependent mechanism. Conceptually, our findings suggested that in addition to hyper-methylation in CpG island at DNA level, cancer cells also develop m6A hyper-methylation at mRNA level to silence tumour suppressor gene expression. Our findings of METTL3-m6A-YTHDF2-SOCS2 pathway exemplified the critical role of m6A epi-transcriptomic change in human carcinogenesis (Chen M et al., Hepatology 2018, 57: 2254). We are currently working on the identification and characterization of novel m6A modified mRNAs and investigating their implications in liver carcinogenesis.
Dr JCM Wong, Department of Pathology
Dr Chun-ming Wong is an associate professor of the Department of Pathology and a Principal Investigator of the State Key Laboratory of Liver Research. He is keen on investigating the genome and epigenome of liver cancer and is one of the pioneers working on RNA modification and liver cancer.
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