The roles and oncogenic mechanisms of RET-finger protein/TRIM27 in human hepatocellular carcinoma

Though hepatocellular carcinoma is the most prevalent malignant disease and leading cause of cancer death in our population, the underlying molecular mechanisms for the development of hepatocellular carcinogenesis remains largely unclear. This is the reason why there is no effective therapy for HCC except mechanical tumor eradication. The long-term goal of our study is to identify the genes and pathways that are essential for hepatocellular carcinogenesis, thereby improving therapeutic efficacy for HCC in future. To this end, we have developed a novel approach identifying genes that are deregulated in HCC (Pan et al. BMC Genomics, 2006; Hsieh et al., Mol Carcinogenesis, 2010; Hsieh et al. HEPATOLOGY, 2011). Of them TRIM27 is of particularly interesting, since it is barely detectable in normal liver but expressed in most of HCC tissues, a character for being therapeutic targets. Expression of TRIM27 was found in 40% of breast cancer and 47% of endometrial cancer and was associated with poor prognosis. However, the role and molecular mechanisms of TRIM27 in carcinogenesis have been never addressed. In our pilot studies, we found: 1) TRIM27 was upregulated in most of the HCC tissues as compared to the corresponding nontumor liver tissues; of note is that TRIM27 is barely detectable in normal liver tissues; 2) silencing of TRIM27 expression suppressed cell proliferation and tumorsphere formation of HCC cells; 3) induction of TRIM27 expression led to disruption of mitotic spindle. To further elucidate the clinical significance of TRIM27 in human HCC and to further investigate the roles and underlying molecular mechanisms of potential oncogenesis of TRIM27 in hepatocellular carcinogenesis, we set forth to a three-year project to achieve the following aims: 1) correlation of overexpression of TRIM27 to the clinical manifestations and outcomes of HCC; 2) clarification of the roles of TRIM27 overexpression in hepatocellular carcinogenesis; 3) Dissection of the molecular mechanisms of oncogenesis of TRIM27; 4) verification of the oncogenesis of RFP in a transgenic mouse model; 5) evaluation of RFP as a candidate marker for poor prognosis of HCC (2nd ~ 3rd yr); 6) evaluation of RFP as a candidate therapeutic target for anti-HCC therapy (2nd ~ 3rd yr).

Project ID:PC10202-0253
External Project ID:NSC100-2314-B182-022-MY3