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Moreover, we identified that RNA binding protein NONO was a direct target of miR-197-5p and miR-197-5p negatively regulated NONO expression and TGF-β signaling in ESCC cells. In summary, our findings suggest that lncRNA FAM225A promotes ESCC development and progression via sponging miR-197-5p and upregulating NONO expression. These results suggest that lncRNA FAM225A could be explored as a new therapy target in ESCC treatment.Background Hepatocellular carcinoma (HCC), a most common malignant tumor, has an unfavorable clinical outcome. E