The Mechanism Of HIF1A Regulating M6A Reader YTHDF2 Promoting Gastric Cancer Progression

Objective and significance: Gastric cancer is one of the most common malignant tumors,but it lacks the specificity of early diagnosis.Most patients with gastric cancer have been found in the middle and late stages,so they have missed the best period of surgical treatment and cannot be radically cured through surgery,which increases the risk of postoperative recurrence and metastasis,leading to poor survival prognosis of patients with gastric cancer.HIF1 A is a protein with a variety of functions,mainly regulating the cell response of tumor hypoxia,its target genes include VEGF gene family,IGF gene family,NF-κB,so that tumor cells in the absence of oxygen to continue proliferation,migration and other biological effects,play an important role in the occurrence and development of most tumors,therefore,In this study,the expression levels of HIF1 A and YTHDF2 in gastric cancer were verified through bioinformatics and cell experiments,and the effect of HIF1 A inducing and regulating YTHDF2 on the proliferation and migration of gastric cancer cells was explored,and the mechanism of HIF1 A regulating YTHDF2 in the progression of gastric cancer was first discussed.It provides important reference value for targeted therapy strategy of gastric cancer.Research methods: Bioinformatics Analysis:This topic used bioinformatics methods to explore the expressions of HIF1 A and YTHDF2 in gastric cancer through online database GEPIA(Gene Expression Profiling Interactive Analysis,GEPIA).Kaplan-Meier online database was used to analyze the relationship between HIF1 A,YTHDF2 and survival prognosis of patients with gastric cancer,and to explore the regulatory effects between them.The correlation between HIF1 A and YTHDF2 and the protein interaction network diagram were verified by STRING.The ID-related data of HIF1 A and YTHDF2 were downloaded from the TCGA database,and the heat map of the co-expression relationship between HIF1 A and YTHDF2 and the relationship with clinically-relevant pathological features was drawn using R language.The Protein expression levels of HIF1 A and YTHDF2 in gastric cancer tissues and the screening of gastric cancer cell lines were analyzed by HPA database(Human Protein Atls).The expression levels of HIF1 A and YTHDF2 in protein and m RNA under normal oxygen and hypoxia were investigated by Western bloot and RT-q PCR,respectively.The effects of HIF1 A and YTHDF2 expression levels on proliferation and migration of gastric cancer patients were investigated through Wound healing and CCK8 testsResults: Both HIF1 A and YTHDF2 were expressed in a variety of cancers,at both protein and m RNA levels,and were higher in cancer tissues than in paracancer tissues(P <0.05),especially in gastric cancer.Both HIF1 A and YTHDF2 were highly expressed in gastric cancer cells(P < 0.05),and their relative expression levels were positively correlated(R =0.53,P < 0.001).The survival prognosis of gastric cancer patients with high expression of HIF1 A and YTHDF2 was worse.HIF1 A and YTHDF2 were highly expressed at the protein level and m RNA level(P < 0.001),and the expression of HIF1 A increased with the increasing concentration of Cocl2,reaching the maximum at 300umol/ml(P < 0.05).The expression of YTHDF2 increased gradually with the increase of HIF1 A,and also reached the maximum when the concentration was 300umol/ml(P < 0.05).The expression of HIF1 A and YTHDF2 in gastric cancer cells was positively correlated,and the expression level of HIF1 A was significantly correlated with the hypoxia of the tumor microenvironment in gastric cancer cells.The higher the degree of hypoxia,the higher the expression,and the higher the expression,the more it could promote the proliferation and migration of gastric cancer cells.Conclusion:HIF1A and YTHDF2 were highly expressed in gastric cancer cells,which may be related to the tumor stage of gastric cancer cells.HIF1 A can promote the expression of YTHDF2 in gastric cancer cells under hypoxia.HIF1 A may induce and regulate YTHDF2 to promote the proliferation and migration of gastric cancer cells.HIF1 A combined with YTHEF2 is expected to be a biomarker and a new therapeutic target for gastric cancer.