MiR-3154 promotes hepatocellular carcinoma progression via suppressing HNF4α.

Abstract

MicroRNAs (miRNAs) play an important role in cancer proliferation, metastasis, drug resistance and apoptosis by targeting oncogenes or tumor suppressor genes. miR-3154 has been reported to be up-regulated in cervical cancer and leukemia, but its role in hepatocellular carcinoma (HCC) remains unclear. Here, we for the first time demonstrated that miR-3154 was elevated in HCC and liver cancer stem cells (CSCs). Up-regulated miR-3154 was associated with overall survival and disease-free survival of HCC patients. MiR-3154 knockdown inhibits HCC cells self-renewal, proliferation, metastasis, and tumorigenesis. Mechanistically, miR-3154 target directly to HNF4α. MiR-3154 knockdown upregulated HNF4α mRNA and protein expression. HNF4α interference abolish the differences of self-renewal, proliferation, metastasis, and tumorigenesis between miR-3154 knockdown cells and control hepatoma cells. Furthermore, miR-3154 expression was negatively correlated with HNF4α in HCC tissues. The combined HHC panels exhibited a better disease-free survival prognostic value for HCC patients than any of these components alone. More importantly, miR-3154 determines the responses of hepatoma cells to lenvatinib treatment. Analysis of patient cohort and patient-derived xenografts (PDXs) further suggest that miR-3154 might predict lenvatinib clinical benefit in HCC patients. In conclusion, we reveal the crucial role of miR-3514 in HCC progression and lenvatinib response, suggesting potential therapeutic targets for HCC.