Dr WONG Chun Ming, Jack
Assistant Professor
BSc HK; MMedSc HK; PhD HK
Cancer epigenetics and molecular pathogenesis of liver cancer
Research Interest
- Epigenetic alterations in liver cancer
- MicroRNA deregulation in liver cancer
- Mechanisms of epigenetic gene regulation
- Epigenetic-miRNA regulatory circuitry
Liver cancer (hepatocellular carcinoma, HCC) is one of the most common malignancies worldwide and is particularly prevalent in Asia. Liver cancer is an aggressive cancer associated with a poor prognosis that is often due to late presentation of symptoms and frequent tumor metastasis. However, the molecular mechanisms underlying hepatocarcinogenesis are unclear. In addition to genetic alterations, recent evidences have indicated that epigenetic abnormalities also play a very important role in hepatocarcinogenesis. Epigenetic, as implied by the Greek prefix, Epi- (means “in addition to”), refers to an additional regulatory layer on top of genetic information stored in DNA sequence. DNA methylation and histone modifications are two major epigenetic events that work very closely in regulating chromatin structure and gene expression pattern. We and others have previously shown that epigenetic alterations play a crucial role in silencing tumor suppressor genes in human cancers. We are interested to elucidate the molecular basis and pathological roles of various epigenetic alterations in human HCC. MicroRNA is a class of small non-coding RNA profoundly involved in post-transcriptional gene regulation and recently implicated in human carcinogenesis. We are also interested to study the expression profiles, epigenetic alterations and molecular functions of microRNAs and their roles in liver cancer development and metastasis. Our recent studies particularly focus on delineating the interplay between miRNA and epigenetic machinery and how deregulation of this epigenetic-miRNA regulatory circuit implicated in liver cancer progression and metastasis. We believe that a better knowledge of the underlying molecular mechanisms of hepatocarcinogenesis and cancer metastasis is of crucial importance for the development of new diagnostic tools and therapeutic interventions for this lethal cancer.
Major research Funding:
- Research Grant Council- General Research Fund (2008-PI, 2011-PI)
- Research Grant Council-Collaborative Research Fund (2010-CoI)
Selected publications:
Click here for detail publication list on PubMed
Gao P, Wong CC, Tung EK, Lee, JM, Wong CM #, Ng IO #. Deregulation of microRNA expression occurs early and accumulates in early stages of HBV-associated multistep hepatocarcinogenesis. J Hepatol, 2011; 54:1177 (# corresponding authors)
Wong CM, Wong CC, Ng YL, Au SL, Ng IO. Transcriptional repressive H3K9 and H3K27 methylations contribute to DNMT1-mediated DNA methylation recovery. PLoS ONE, 2011, 6: e16702
Wong CC *, Wong CM *, Tung EK, Au SL, Lee, JM, Poon RT, Man K, Ng IO. The microRNA MiR-139 suppresses metastasis and progression of hepatocellular carcinoma by downregulating Rho-kinase 2. Gastroenterology. 2011; 140:332. (*Wong CC and Wong CM contributed equally to this work.)
Liang L, Wong CM, Ying Q, Fan DN, Huang S, Ding J, Yao J, Yan M, Li J, Yao M, Ng IO, He X. MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology. 2010; 52:1731
Ko FC, Yeung YS, Wong CM, Chan LK, Poon RT, Ng IO, Yam JW. Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma. Liver Int. 2010: 30:139-48
Wong CC, Wong CM, Tung EKK, Man K, and Ng IO. Rho-kinase 2 (ROCK2) is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion. Hepatology. 2009; 48:1583
Tung EKK, Wong CM, Yau TO, Lee JM, Ching YP and Ng IO. HAI-2 is epigenetically down-regulated in human hepatocellular carcinoma and its Kunitz domain type 1 is critical for its anti-invasive function. Int J Cancer. 2009; 124:1811
Wong CC, Wong CM, Ko FC, Chan LK, Ching YP, Yam JW, Ng IO. Deleted in liver cancer 1 (DLC1) negatively regulates Rho/ROCK/MLC pathway in hepatocellular carcinoma. PLoS ONE. 2008; 3:e2779.
Lee JM, Wong CM and Ng IO. Hepatitis B virus-associated multistep hepatocarcinogenesis: a stepwise increase in allelic alterations. Cancer Res. 2008; 68:5988-96.
Wong CM, Ng YL, Lee JM, Wong CC, Cheung OF, Chan CY, Tung EK, Ching YP, Ng IOL. Tissue factor pathway inhibitor-2 as a frequently silenced tumor suppressor gene in hepatocellular carcinoma. Hepatology 2007; 45: 1129-1138.
Leung TH, Ching YP, Yam JW, Wong CM, Yau TO, Jin DY, Ng IO. Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity. Proc Natl Acad Sci U S A. 2005; 102:15207-15212
Wong CM*, Yam JW*, Ching YP, Yau TO, Leung TH, Jin DY, Ng IO. Rho GTPase activating protein DLC1 (deleted in liver cancer) suppresses cell proliferation and invasion in hepatocellular carcinoma. Cancer Res 2005; 65: 8861-8868(*Wong CM and Yam JWP contributed equally to this work.)
Chin KT, Zhou HJ, Wong CM, Lee JM, Chan CP, Qiang BQ, Yuan JG, Ng IO, Jin DY. The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma. Nucleic Acids Res 2005; 33:1859-1873
Yau TO, Chan CY, Chan KL, Lee JM, Wong CM, Fan ST, Ng IO. HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently downregulated in hepatocellular carcinoma: involvement of methylation-mediated gene silencing. Oncogene 2005; 24:1607-1614
Chan CF, Yau TO, Jin DY, Wong CM, Fan ST, Ng IO. Evaluation of nuclear factor-kB, urokinase-type plasminogen activator (uPA) and HBx and their clinicopathological significance in hepatocellular carcinoma. Clin Cancer Res 2004; 10: 4140-4149.
Pang R, Yuen J, Yuen MF, Lai CL, Lee TK, Man K, Poon RT, Fan ST, Wong CM, Ng IO, Kwong YL, Tse E. Pin1 overexpression and b-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma. Oncogene 2004; 23: 4182-4186.
Wong CM, Lee JM, Ching YP, Jin DY, Ng IO. Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer Res. 2003; 63: 7646-7651.
Ching YP*, Wong CM*, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO. Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma. J. Biol. Chem. 2003; 278:10824-10830. (*Ching YP and Wong CM contributed equally to this work.)
Wong CM, Lee JM, Lau TC, Fan ST, Ng IO. Clinicopathological significance of loss of heterozygosity on chromosome 13q in hepatocellular carcinoma. Clin. Cancer Res. 2002; 8: 2266-2272.
Wong CM, Fan ST, Ng IO. ß-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance. Cancer 2001; 92: 136-145.
Review articles:
Wong CC, Wong CM, Au SL, Ng IO. RhoGTPases and Rho-Effectors in Hepatocellular Carcinoma Metastasis: ROCK N' Rho Move It. Liver Int. 2010; 30:642
Yam JY, Wong CM, Ng IO. Molecular and functional genetics of hepatocellular carcinoma. Front Biosci (Schol Ed). 2010; 2:117-34
Wong CM and Ng IOL. Molecular pathogenesis of hepatocellular carcinoma. Liver Int. 2008; 28:160-174.
Book chapters:
Wong CM, Yam JW and Ng IO, Molecular Pathogenesis of Hepatocellular, In: Wang XW et al. (eds), Molecular Genetics of Liver Neoplasia, Cancer Genetics, Springer, 2010
Yam JW, Wong CM and Ng IO, Deleted in liver cancer 1 (DLC1), In: Schwab M, Encyclopedia of Cancer. Springer, 2008, 2nd Ed