Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for liver CSCs expansion remains unclear. Herein, we report that miR-124 is downregulated in liver CSCs and associated with the poor prognosis of HCC. Functional studies revealed that a forced expression of miR-124 inhibits liver CSCs self-renew and tumorigenesis. Conversely, miR-124 knockdown promotes liver CSCs self-renew and tumorigenesis. Mechanistically, miR-124 directly target Caveolin-1 (CAV1) via its mRNA 3'UTR in liver CSCs. Furthermore, miR-124 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohort and patient-derived xenografts (PDXs) further demonstrated that miR-124 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-124 in liver CSCs expansion and sorafenib response, rendering miR-124 an optimal target for the prevention and intervention in HCC.
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