The Role Of HIF-2in Renal Cancer Cell Growth And Metastasis Promoted By HPPCn

Objective and significance:Hepatopoietin Cn is a mammalian liver regeneration of new cell growth factor, is widelyexpressed in many tissues. Nuclear protein as a kind of multifunctional, itmainly in normal tissues and tumor tissues expressing cells self-renewal, and is involved in signaltransduction, cell protein degradation, cytoskeleton dynamics and cell mormmorphogenesis and other biological process.In CRCC cells of target gene transcriptiotranscription of HIF-1α and HIF-2α are not exactly the same, and clearly defines the specifictarget gene of HIF-1α and HIF-2α. Many cancer genes such as CyclinD1,TG F-α, VEGF isa specific target gene of HIF-2α, and pro-apoptotic gene BNIP3is a sp ecific target gene ofHIF-1α. And HIF-1α and HIF-2α with different signal transduc ction pathways linking.Activation of HIF-1α can inhibit c-Myc dependent cell prolif feration, while HIF-2α rolein contrast. In addition, HIF-1α was more sensitive than HIF-2α degradation of proteaseVHL deletion of CRCC cells in the body. Multiple v ascular feature of CRCC is closelyrelated to the upregulation of HIF-2and CRCC, high expression of HIF-1α patients survivalperiod is longer than other types of patie ents. Therefore, HIF, especially in the developmentof CRCC HIF-2α may play a mor more Recent studies have found that closely related to thegrowth and prognosis of H PPCn expression and activity and tumor. HPPCn can inhibit avariety of chemootherchemotherapeutic drugs (Sorafinib, ADM, CDD, TSA) hepatocellular carcinoma cellapoptosis induced by tumor cells, and can promote the epithelial-mesenchymal transtransition through the regulation of the expression of miRNA (EMT) and migration ofvascular endothelial cells, promote tumor metastasis and invasion. Liver cancer induc ed by transgenic mice showed that HPPCn in the induction of early increased express ion ofproto-oncogene c-myc, and a significant increase in the rate of lung metastasis of tumor.Hepatoma cells by tail vein injection experiments showed high expression of HPPCn canincrease the number of vascular lung metastasis and tumor cells. So tha t what is the relationbetween HPPCn and HIF? There will be what kind of relations hip, development of HPPCnand renal cell carcinoma?Effect and mechanism of HPPCn regulation of HIF-2a we study the growth andmetastasis of renal cell carcinoma cells to promote. To do the research work as followMethods:Construct lentiviral vector interfered with HIF-2, apply Western blot and Q-PCR to detectinterference efficiency of HIF-2. Then the tumor cells interfering with the expression ofHIF-2, apply MTS, scratch test, Transwell experiment to detect the role of HIF-2in thedevelopment of renal cancer cells promoted by HPPCn.Results:We construct PLKO.1-shHIF-2through lentiviral vector technology, and packaged intolentivirus, it can effectively interfere with the expression of HIF-2in cells, interferingefficiency in protein and mRNA levels were greater than80%, after cloning expandingculture, access to786-0cells stably interference HIF-2, laid the foundation for the study ofthe function of HPPCn.Secondly, we verified HPPCn regulates HIF-2of renal clear cell carcinoma to affect thebiological characteristics of renal cell carcinoma. We interference with stable HIF-2786-0cells to carry out experiments to prove that interfered with the expression of HIF-2in the786-0cells, HPPCn protein on cell proliferation, migration, apoptosis rate were gone.In summary, our results indicate that HPPCn regulates HIF-2a plays a very important rolein the process of tumor progression, the results will be for the treatment of renal clear cellcarcinoma provide new therapeutic targets...