Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A
Abstract Hepatocellular carcinoma (HCC) is a malignant cancer worldwide; lacking biomarkers for early prognostication contributes to its high lethality. Herein, we report a novel biomarker, exosome delivered miR-93, is up-regulated in HCC cell line media and serum samples of HCC patients. We measured the proliferation and invasion ability of HCC cell lines following exosomal miR-93 treatment. After prediction with online algorithms, we further confirmed that TP53INP1, TIMP2 and CDKN1A are direct targets of miR-93 by dual-luciferase reporter assay. In addition, the diagnostic value of exosomal miR-93 was evaluated by qPCR and ROC analysis. The significant correlation between serum exosomal miR-93 and clinical information including stage, tumor size were observed. Furthermore, the survival differences of HCC patients with high or low miR-93 were statistically significant using Kaplan-Meier analysis. In summary, our work identified exosomal miR-93 as a novel biomarker for both diagnosis and prognosis in HCC. Highlights Exosomal miR-93 is up-regulated both in HCC cell lines' media and HCC patients' serum. Exosomal miR-93 promotes HCC proliferation and invasion by regulating TIMP2/TP53INP1/CDKN1A. Exosomal miR-93 is correlated with clinical information including stage, tumor size and predict patients' survival rate.
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