The Therapeutic Targets of miRNA in Hepatic Cancer Stem Cells

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide malignancy and the third leading cause of cancer death in patients. Several studies demonstrated that hepatic cancer stem cells (HCSCs), also called tumor-initiating cells, are involved in regulation of HCC initiation, tumor progression, metastasis development, and drug resistance. Despite the extensive research, the underlying mechanisms by which HCSCs are regulated remain still unclear. MicroRNAs (miRNAs) are able to regulate a lot of biological processes such as self-renewal and pluripotency of HCSCs, representing a new promising strategy for treatment of HCC chemotherapy-resistant tumors. In this review, we synthesize the latest findings on therapeutic regulation of HCSCs by miRNAs, in order to highlight the perspective of novel miRNA-based anticancer therapies for HCC treatment.

Figure 1

Key signaling pathways that regulate the function of hepatic cancer stem cells. The cartoon recapitulates the principle signaling pathways that regulate the function of hepatic CSCs such as Wnt/β-catenin, Hedgehog, and Notch. Epithelial cell adhesion molecule (EpCAM) is a Wnt/β-catenin signaling target gene. The activation of Wnt/β-catenin signaling regulates EpCAM expression in HCSCs. In CD133⁺ HCC cells, Wnt/β-catenin, Notch1, and smoothened (SMO)/Hedgehog signaling pathways are associated with proliferation, self-renewal, and differentiation of HCSCs.