Exploring Expression And Significance Of HNRNPU In Hepatocellular Carcinoma Based On Multi-omics

Objective: Hepatocellular carcinoma(HCC)is a common malignant digestive system tumors.HCC is the sixth most common malignant tumor and fourth most common cause of cancer-related deaths worldwide.It has high morbidity,high mortality,and high metastasis rate and high recurrence rate.According to the latest global cancer statistics,the number of new cases of liver cancer worldwide was841,000,and the number of deaths was 782,000 in 2018.More than 50% of new cases and deaths were from China.Although many genes related to the development of HCC have been identified in the past decade,the specific mechanism of HCC formation remains unclear.This study aims to identify key genes and key pathways in the development of HCC through the GEO and TCGA databases,and explore the molecular mechanisms of HCC formation through cell experiments.Methods: We analyzed six HCC-related datasets(GSE14520_GPL571?GSE14520_GPL3921 ? GSE41804_GPL570 ? GSE45267_GPL570 ? GSE60502_GPL96 ?GSE6764_GPL570)from the GEO database,and screened HNRNPU closely related to the occurrence and development of HCC through meta-analysis and pathway analysis.We analyzed the differential expression of HNRNPU in HCC tissues and normal tissues,and the relationship between HNRNPU expression levels and various clinicopathological features of HCC patients.we Analyze the ability of HNRNPU expression level to predict the occurrence or not of HCC.In addition,we also analyzed the molecular mechanism of HNRNPU in the development of HCC and the effect of shHNRNPU on HCC cell proliferation.Results: Bioinformatics analysis showed that HNRNPU was closely related to the occurrence and development of HCC.The expression level of HNRNPU in HCC tissues was significantly higher than that in normal tissues(P1<0.001,P2<0.001,P3<0.001,P4<0.001,P5= 0.001,P6<0.001),and the analysis of TCGA data also confirmed this conclusion(t =-7.32,P<0.001).In addition,meta-analysis of these six microarray data was performed using a fixed-effects model.HNRNPU was highlyexpressed in hepatocellular carcinoma tissues,and the difference was also significant(SMD=1.61;95% CI=1.43-1.78;P<0.001).The expression level of HNRNPU in the low age group was significantly higher than that in the high age group(t=3.216,P=0.001).The expression level in the G3-G4 group was significantly higher than that in the G1-G2 group(t=-5.701,P<0.001).The ROC curve indicates that the use of HNRNPU expression level to predict the occurrence of HCC has a higher diagnostic value(AUC=0.796).In addition,this study also found that HNRNPU affects the development of HCC by affecting the expression of related genes in cell cycle,metabolism,and developmental pathways.Cell experiments showed that knockdown IMP3 expression in SMMC7721 and Huh7 cell lines could significantly inhibited HCC cell proliferation(PHuh7=0.00016,PSMMC7721= 0.00036).Conclusions: HNRNPU is highly expressed in HCC tissues,and HNRNPU expression level is closely related to cell proliferation and HCC development.This study suggests that HNRNPU may be used as a biomarker to provide new strategies for the prevention,early diagnosis and treatment of HCC.