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.

肝癌干细胞（CSC）有助于肝细胞癌（HCC）的肿瘤发生，进展，复发和耐药性。但是，肝CSCs扩展的潜在机制仍不清楚。本文中，我们报道miR-124在肝CSC中被下调，并与肝癌预后不良有关。功能研究表明，miR-124的强制表达抑制肝脏CSC的自我更新和肿瘤发生。相反，miR-124敲低可促进肝CSC的自我更新和肿瘤发生。从机制上讲，miR-124通过其mRNA 3'UTR在肝CSC中直接靶向Caveolin-1（CAV1）。此外，miR-124的表达决定了肝癌细胞对索拉非尼治疗的反应。对患者队列和患者异种移植物（PDXs）的分析进一步表明，miR-124可能预测索拉非尼在肝癌患者中的获益。