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Investigation On The Effect And Mechanism Of PIKE-A Promoting The Development And Progression Of Glioma

Posted on:2020-04-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:H ShengFull Text:PDF
GTID:1484306542468424Subject:Biology Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Glioma has been listed as one of the top ten malignant tumors in recent global tumor statistics.As a oncogene in glioma,PIKE-A must play an important role in the regulation of the occurrence and development of glioma.Therefore,the effects of PIKE-A on rapid growth of glioma must also conform to one of the ten characteristics of tumor cells-metabolic disorder,but the specific regulatory mechanism having not been reported.In this study,we constructed a stable PIKE-A knockdown' cell line through lentivirus to study how PIKE-A regulates cell metabolism to meet the requirement of rapid growth.After the knockdown of PIKE-A,both in vivo and in vitro experiments confirmed that the proliferation capacity of tumor was significantly reduced;Immunoblotting results confirmed that the level of 705 site tyrosine phosphorylation of STAT3,and the expression of G6 PD,a key enzyme in the pentose phosphoric acid metabolic pathway,were decreased in glioma cells with PIKE-A knocked down;The dual fluorescence reporter results confirmed that PIKE-A /STAT3 can regulate the activity of G6 PD promoter;Fluorescence staining'data showed that the ability of DNA synthesis decreased when PIKE-A was knockdown;Flow cytometry' results confirmed that ROS increased with PIKE-A knocked down;The results of colorimetry confirmed that the intracellular NADPH/NADP+ ratio decreased with PIKE-A knocked down;?-galactosidase staining' data confirmed that cell senescence increased with PIKE-A knocked down.In this study,we found for the first time that PIKE-A can regulate the level of phosphorylation of STAT3,and found that STAT3 can regulate the activity of G6 PD promoter to regulate the expression of G6 PD m RNA,which promoting the rapid growth of glioma.
Keywords/Search Tags:glioma, PIKE-A, STAT3, G6PD, Aging, ROS, Promoter
PDF Full Text Request
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