miR-552 Regulates Liver Tumor-Initiating Cells Expansion and Sorafenib Resistance

Abstract MicroRNAs (miRNAs) are involved in tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, few miRNAs have been identified and entered clinical practice. Herein, we report that miR-552 is upregulated in HCC tissues and has an important function in liver tumor-initiating cells (T-ICs). Functional studies revealed that a forced expression of miR-552 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, miR-552 knockdown inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-552 downregulates PTEN via its mRNA 3'UTR and activates AKT phosphorylation. Our clinical investigations elucidated the prognostic value of miR-552 in HCC patients. Furthermore, miR-552 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrated that miR-552 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-552 in liver T-ICs expansion and sorafenib response, rendering miR-552 an optimal target for the prevention and intervention in HCC.