LiFu Hu Project Group

Epigenetic change and disease

Epigenetic changes in initiation and development of cancers

Epigenetics refers to the study of heritable changes in gene expression without a change in DNA sequence. It is critical for normal development and growth of cells. In cancer, silencing of tumor suppressor genes (TSG) or activation of oncogene, being a main mechanism for carcinogenesis, is often caused by aberrant DNA methylation of CpG islands and histone hypoacetylation in early stage of cancer, affecting various fundamental pathways, such as apoptosis, invasion and metastasis.

We found that the cellular gene RASFF2 and CDH13 works as tumor suppressor genes via promoter hypermethylation and is linked to clinical outcome of nasopharyngeal carcinoma (NPC) as a tumor model while the oncogene BAGE is activated by hypomethylation. Cancer related EB virus also uses the epigenetic mechanism to maintain virus latency and regulate the expression of both viral and cellular gene by EBV encoded LMP1 oncogene.

Aiming at an early diagnosis, we have identified novel TSGs by methylation and expression microarrays, and developed a sensitive Multiplex Methylation Specific PCR (MMSP) for NPC on mouth washing/swab samples. It was patented in Australia 2008 and is in clinical trail. The same strategy was designed to detect prostate/bladder and lung cancers from urine, and sputum samples respectively.

Micro RNAs (miRNAs) are approximately 22nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translation inhibition or messenger RNA degradation, which contributes cancer development and progression. Function of miRNAs in tumor progression, regulation by epigenetic alteration, and potential application for diagnosis of NPC are being explored. The EBV encoded, non-coding RNA (170bp), EBERs, which are expressed abundantly and constitutively in nucleus of all latently infected cells, are also studied.

Selected Publications

Identification of characteristic and prognostic values of chromosome 1p abnormality by multi-gene fluorescence in situ hybridization in multiple myeloma.
Li F, Hu L, Xu Y, Li Z, Yi S, Gu Z, et al
Leukemia 2016 May;30(5):1197-201

Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.
Nawaz I, Hu L, Du Z, Moumad K, Ignatyev I, Pavlova T, et al
Oncotarget 2015 Oct;6(31):31493-507

Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay.
Nawaz I, Moumad K, Martorelli D, Ennaji M, Zhou X, Zhang Z, et al
Clin Epigenetics 2015 ;7():89

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer.
Nawaz I, Qiu X, Wu H, Li Y, Fan Y, Hu L, et al
Epigenetics 2014 Aug;9(8):1138-48

Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma.
Zhang Z, Sun D, Hutajulu S, Nawaz I, Nguyen Van D, Huang G, et al
PLoS ONE 2012 ;7(11):e45908

Clinical significance of elevated spleen tyrosine kinase expression in nasopharyngeal carcinoma.
Du Z, Kou C, Wang H, Huang M, Liao D, Hu C, et al
Head Neck 2012 Oct;34(10):1456-64

Genomic DNA hypomethylation by histone deacetylase inhibition implicates DNMT1 nuclear dynamics.
Arzenani M, Zade A, Ming Y, Vijverberg S, Zhang Z, Khan Z, et al
Mol. Cell. Biol. 2011 Oct;31(19):4119-28

Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
Du Z, Hu L, Wang H, Yan L, Zeng Y, Shao J, et al
PLoS ONE 2011 Apr;6(4):e19137

Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma.
Zhang Z, Sun D, Hutajulu S, Nawaz I, Nguyen Van D, Huang G, et al
PLoS ONE 2012 ;7(11):e45908

Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker.
Sun D, Zhang Z, Van D, Huang G, Ernberg I, Hu L
Oral Oncol. 2007 Jan;43(1):82-7

Senior researcher

Li-Fu Hu

Organizational unit: Ingemar Ernberg group