The Identification And Functional Exploration Of Fusion Gene Ppsh In Hepatocellular Carcinoma

Primary liver cancer (PLC) is the eighth largest cancer in the world, which hasabout1million new cases and leads to500thousand deaths every year[1]. As one ofthe most common cancers in the world, the proportion of Hepatocellular, Carcinoma(HCC) in adult PLC is about80-90%. Five-year survival rate of hepatocellularcarcinoma in USA is only8.9%[2], epidemiological investigation revealed manyrelevant factors of primary liver cancer, such as hepatitis B and hepatitis C virusinfection, excessive drinking, eating food containing aflatoxin B1[3], but there areabout50%of PLC being caused by HBV infection [4]; after decades studing, a lot ofprogress in driving the molecular mechanism of hepatocarcinogenesis has been made,and many genes are found to have an important relationship with the occurrence anddevelopment of HCC, such as tumor suppressor genes (TP53,[5], p16and p21) andthe cancer promoting gene (β-catenin[6], ErbB family [7], COX-2[8] and HGF[9]).In addition, liver cancer cells can produce many genomic changes, includingchromosome instability, CpG island methylation, DNA rearrangement, nucleotidesubstitution and microsatellite instability, somatic cell genetic aberration has beenproved to be the initial factor of the occurrence and development of tumors, includingsingle base substitutions, translocation and genomic copy number changes of [10],and chip technology has been applied to the cell genomic changes [11-12].The second generation sequencing technology (Next generation sequencing,NGS) provide a particular and specific mass genomic data of tumor cells at a lowprice, as a result NGS provides a convenient way for genome analysis of tumor tissue.Recently, it has been reported that the whole genome sequencing of acutemyelogenous leukemia has already completed by Illumine/Solexa sequencing, whichprovides a good platform and tool for the further study of the cancer genome [13].It was in1960that Nowell and Hungerford first reported the Philadelphiachromosome found in chronic myelogenous leukemia. It was proved that thePhiladelphia chromosome was caused by BCR-ABL gene fusion in1973by Rowley,which motivated great interest of scientists to explore the relationship between fusiongene and tumors[14]. In the past3decades, more and more fusion genes have beenreported in some blood malignancies and sarcoma, such as: sarcoma, thyroid tumor,renal cancer, prostate cancer, non-small cell lung cancer, etc. and some benign tumor, such as lipoma and leiomyosarcoma. But the existence of fusion genes found inhepatocellular carcinoma (HCC) is relatively rare.In this study, it is the first time for us to use the second generation sequencingtechnology to analyze HCC samples and found that gene fusion phenomenonhappened in region11q13.2-13.3which is closely related with the prognosis of livercancer, suggesting that this fusion gene may play a role in the development of livercancer. Based on this background, we focus on the fusion gene ppsh and supposed tofind out its role and mechanism in HCC，providing more theoretical basis inunderstanding the pathogenesis and therapeutic targets of HCC.Conclusion:It is the first time to identify a new fusion gene ppsh in Hepatocellular Carcinomaand prove that ppsh can promote liver cancer cell metastasis and invasion in vivo andvitro. PPSH can activate p38pathway through the interaction with hsp90and PSMB1,then promote activation of ATF2and HSP27in p38pathway download, ultimatelypromote the expression of MMPs working for liver cancer cell metastasis andinvasion.