HPPCn Regulation Of HIF-2a Catalytic Effects And Mechanism Of Renal Carcinoma Cell Growth And Metastasis

Objective and significance:Hepatopoietin Cn is a mammalian liver regeneration of new cell growth factor, iswidely expressed in many tissues. Nuclear protein as a kind of multifunctional, itmainly in normal tissues and tumor tissues expressing cells self-renewal, and is involvedin signal transduction, 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 thespecific target gene of HIF-1α and HIF-2α. Many cancer genes such as CyclinD1,TGF-α, VEGF is a specific target gene of HIF-2α, and pro-apoptotic gene BNIP3is a specific target gene of HIF-1α. And HIF-1α and HIF-2α with different signal transducction pathways linking. Activation of HIF-1α can inhibit c-Myc dependent cell prolifferation, while HIF-2α role in contrast. In addition, HIF-1α was more sensitive thanHIF-2α degradation of protease VHL deletion of CRCC cells in the body. Multiple vascular feature of CRCC is closely related to the upregulation of HIF-2and CRCC,high expression of HIF-1α patients survival period is longer than other types of patieents. Therefore, HIF, especially in the development of CRCC HIF-2α may play a mormore Recent studies have found that closely related to the growth and prognosis of HPPCn expression and activity and tumor. HPPCn can inhibit a variety of chemoother chemotherapeutic 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 induced by transgenic mice showed that HPPCn in the induction of early increased expression of proto-oncogene c-myc, and a significant increase in the rate of lung metastasisof tumor. Hepatoma cells by tail vein injection experiments showed high expressionof HPPCn can increase the number of vascular lung metastasis and tumor cells. So that what is the relation between HPPCn and HIF? There will be what kind of relationship, development of HPPCn and 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:the expression of HPPCn application of Western blot detection of renal clear cellcarcinoma, immunohistochemistry study on renal pathological sections; by lentivirusvector construction method, construction of lentiviral vectors HPPCn inter ferometry;influence of the application of Western blot detection of HPPCn on the a expressionof HIF-2a, expressed by the interference of tumor cells HPPCn, MTS candetection of cell proliferation, migration of scratch test, Transwell test cell; flow thecytometry cell apoptosis.Results:we found expression in renal clear cell carcinoma was significantly higher thanthat in normal kidney tissues.23cases of renal cell carcinoma immunohistochemistryanalysis showed HPPCn in renal clear cell carcinoma was significantly higher thanthat in paracancerous tissues and normal kidney tissues. At the same time, we alsoconstructed HPPCn interference vector PLKO.1/RFP/shRNA, interference in proteinlevel rate reached75%, and obtained stable interferometric HPPCn786-0/si-HPPCncells by puromycin, laid the foundation for the study of the function of HPPCn.Secondly, we studied the effects of HPPCn on the expression of HIF2a in renalclear cell carcinoma and renal cell carcinoma cell characteristics. HPPCn can upregulate the expression of HIF2a in renal clear cell carcinoma. We through theexpression of interferometric HPPCn tumor cells, demonstrated down-regulation ofHPPCn expression can inhibit cell proliferation, increased cell apoptosis, inhibition ofcell migration, enhance the sensitivity of cells to Sorafinib.In summary, our results indicate that HPPCn regulates HIF2a plays a veryimportant role in the process of tumor progression, the results will be for the treatmentof renal clear cell carcinoma provide new therapeutic targets.