The HIF-1A/miR-17-5p/PDCD4 Axis Contributes To The Tumor Growth And Metastasis Of Gastric Cancer

THESIS: The HIF-1A/mi R-17-5p/PDCD4 axis contributes to thetumor growth and metastasis of gastric cancer SPECIALITY: Biochemistry and Molecular Biology POSTGRADUATE: Zhao Jiayu MENTOR: Professor Chenyu ZhangGastric cancer(GC)is a common malignant tumor worldwide and burdens Asian populations in particular.Programmed cell death 4(PDCD4)is a new-found tumor suppressor gene whose downregulation leads to GC tumorigenesis.However,the underlying mechanism remains unclear.micro RNAs(mi RNAs)can contribute to cancer development by negatively regulating protein-coding genes.mi R-17-5p is an important biomarker for GC whose function is not fully understood.In this study,we explored the correlation between PDCD4 and mi R-17-5p during the oncogenesis of GC progression and investigated how they affected GC progression.As a result,PDCD4 was significantly downregulated while mi R-17-5p was overexpressed in GC patients.An inversely correlation between PDCD4 and mi R-17-5p was identified.Both of them were closely related to the overall and recurrence-free survival of GC patients.mi R-17-5p directly bound to the 3' untranslated region(3'UTR)of PDCD4 and inhibited PDCD4 gene expression,which increased GC proliferation and migration and decreased GC apoptosis in vitro.The suppression by mi R-17-5p on PDCD4 also promoted GC xenografted tumor growth in vivo.Furthermore,HIF-1A was found to drive the transcription of mi R-17-5p by binding to the promoter.These results indicate the critical role of HIF-1A/mi R-17-5p/PDCD4 regulatory axis in GC development and could provide potential targets for GC therapy.