Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and ranks third in the leading causes of cancer patient’s death. Cancer stem cells (HSCs), also known as tumor-initiating cells, have been reported in multiple subtypes of HCC and are considered as the master regulators of HCC initiation, chemotherapy drug resistance, tumor metastasis, and progression. In spite of their clinical importance, the detailed mechanism about how HSCs are intricately regulated in the molecular level remains elusive. MicroRNA (miRNA), a class of newly emerging small noncoding RNAs, has been demonstrated to serve as a vital player in modulating a number of biological activities ranging from embryogenesis to programmed cell death as well as the maintenance of HSCs. In this review, we synthesize these latest findings of miRNA regulation of HSCs and try to elucidate their mechanistic roles in orchestrating cellular equilibrium. This recent progress underlies the functional role of miRNA in cellular transformation of liver cancer, which has largely extended our knowledge how HSCs are controlled by miRNA network, and in the development of novel miRNA-based anticancer therapies specifically targeting HSCs in the coming future.
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