The Expression And Function Analysis Of HIF-1α And Its Related Molecular Signaling Pathways In Pancreatic Cancer

In recent years, the incidence of pancreatic cancer presents a clear upward trendin our country, accounting for2.2%of systemic cancer. However, due to difficulties inearly diagnosis and the high degree of malignancy, the5-year survival rate of pancreaticcancer is still less than5%. There is no improvement in nearly four decades. Therefore,the research of pathogenesis, prevention and treatment about pancreatic cancer is urgent.Related studies have shown that the change of energy metabolism in cells becomean important factor of cell canceration. Sugar metabolism, for example, in themetabolism of normal cells to adapt to low oxygen microenvironment to anaerobicmetabolism mainly for the transition from aerobic metabolism. But the tumor cells isdifferent. Regardless of the adequacy of oxygen in the microenvironment, most of thetumor cell would choose a glycolysis reaction to gain energy for the biological behaviorlike proliferation, invasion and so on. This kind of glycolytic metabolism as the mainway was known as the Warburg effect. Under normal oxygen partial pressure, HIF-1αis rapidly degraded by proteasomes mediated by proline hydroxylase. When the tumorcells proliferate rapidly, the Warburg effect makes a pseudo hypoxic microenvironment,which makes the proline hydroxylase activity decreased, HIF-1α can not be degradedand accumulated in the cytoplasm. With HIF-1β to form a heterodimeric HIF-1. TheHIF-1as a transcription factor, recognition, binding at the genomic hypoxia responseelement, starting the tumor-associated transcription of target genes. These genes areassociated with tumor glycolysis, proliferation, invasion, apoptosis and other acts.Many scholars have confirmed the high expression of HIF-1α in pancreatic cancertissue and pancreatic cancer cell lines. Therefore, HIF-1α as a entry point to study theoccurrence and development of pancreatic cancer can make a big difference. However, cancer is an extremely complex systemic disease, the relatedmetabolites, genes and proteins constitute a complex signaling gene regulatorynetworks. The target genes of HIF-1αarenotonlyinlargerquantities,buttheregulatorymechanism is very complex, it can not be validated by the traditional method ofbiological experiments separately. But the regulatory network of HIF-1α in pancreaticcancer is not yet clear now. In recent years, the rapid development of bioinformaticsmakes the large data analysis possible. Therefore, we take advantage of molecularbiology and bioinformatics, screening differential gene expression in pancreatic cancerby DNA microarray, then we got875differential genes. With transcription factorinformation database, we establishmented HIF-1α signal-regulated network inpancreatic cancer, then we made a function enrichment analysis of these genes,discussing the relationship between HIF-1α andMYC, MYB,SP1,TFAP2A,ESR1andHK2. We analysed the mechanism of HIF-1α regulation of the biological behavior ofpancreatic cancer cells and molecular mechanisms, It may provide some new ideas inpancreatic cancer research.