microRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1.

Abstract

The existence of cancer stem cells is considered as a direct reason for the failure of clinic treatment in hepatocellular carcinoma. Growing evidences have demonstrated that microRNAs play an important role in regulation of stem cell proliferation, differentiation and self-renewal, and their aberrances cause the formation of cancer stem cells and eventually result in carcinogenesis. We recently identified microRNA-148b as one of the microRNAs specifically down-regulated in side population cells of PLC/PRF/5 cell line. However, it remains elusive how microRNA-148b regulates cancer stem cell properties in hepatocellular carcinoma. In this study, we observed that over-expression or knock-down of miR-148b through lentiviral transfection could affect the proportion of side population cells as well as cancer stem cell-related gene expression in hepatocellular carcinoma cell lines. In addition, miR-148b blocking could stimulate cell proliferation, enhance chemosensitivity, as well as increase cell metastasis and angiogenesis in vitro . More importantly, miR-148b could significantly suppress tumorigenicity in vivo . Further studies revealed that Neuropilin-1, a transmembrane coreceptor involved in tumor initiation, metastasis and angiogenesis, might be the direct target of microRNA-148b. Taking together, our findings define that miR-148b might play a critical role in maintenance of side population cells with cancer stem cell properties by targeting Neuropilin-1 in hepatocellular carcinoma. It is the potential to develop a new strategy specifically targeting hepatic cancer stem cells through restoration of miR-148b expression in future therapy.