Abstract: Objective To investigate the effect of miR-200 family members on the prognosis of different tumors and the mechanism of target gene regulation heterogeneity. Methods The transcriptome data and clinical phenotypes of 21 different histopathological malignant solid tumor samples from the PanCanAtlas were downloaded from the Cancer Genome Atlas（TCGA），and the relationship between miR-200 family members and tumor prognosis were analyzed. Five tumors with contradictory survival risk assessment results were further selected for WGCNA cluster analysis of miR-200 family target genes.The expression of target genes significantly related to miR-200 family expression in bladder cancer tissues was verified by immunohistochemistry and fluorescent quantitative PCR，and their effects on patient survival were analyzed. Results The high expression of miR-200 family was a protective factor for the prognosis of bladder cancer and gastric adeno-carcinoma（HR=0.55~0.68，P=0.0001~0.0340；HR=0.61~0.72，P=0.0055~0.0170），and a negative factor for the prognosis of liver cancer and thymoma（HR=1.46~1.65，P=0.0061~0.0120；HR=7.44~13.04，P=0.0002~0.0210），while miR-141 and miR-429 had opposite effects on the survival of renal papillary cell carcinoma. Furter clustering of miR-200 family target gens showed that the expression of TIMP2 gene increased the survival time of bladder cancer patients，and miR-141 prolonged the survival of the patients with renal papillary cell carcinoma by negatively regulated EPHA2 gene. TIMP2 protein expression in bladder cancer was negatively correlated with miR-200 family expression and patients with high expression had better prognosis. Conclusion miR-200 family had different effects on the prognosis of different tumors，and the heterogeneity of miR-200 family targeted molecules results to the heterogeneity of biological function of miR-200 family in cancers.

Key words: miR-200 family, Targeted molecules, Pan-cancer, Heterogeneity