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.