MicroRNA­486­5p functions as a tumor suppressor of proliferation and cancer stem­like cell properties by targeting Sirt1 in liver cancer.

Cancer stem­like cells (CSCs) are critical for the initiation, progression, chemoresistance and postsurgical recurrence of liver cancer. They are thought to be novel targets for the treatment of liver cancer, however, efficient agents that target liver cancer stem cells (CSCs) have not been identified. MicroRNAs (miRNAs) are small non­coding RNAs that target the 3'untranslated region (3'UTR) of mRNAs. Their dysregulation has been implicated in several types of cancer including liver cancer, but it still remains unknown if they play a role in targeting liver CSCs. We compared the miRNA profiles between liver cancer samples and adjacent non­tumor tissues using The Cancer Genome Atlas (TCGA) datasets. Several miRNAs including miR­486­5p (miR­486) were found to be significantly downregulated in liver cancer tissues. These differentially expressed miRNAs were screened between CSC­enriched tumor spheres and adherent cells. miR­486 was significantly downregulated in tumor spheres and liver cancer samples. Ectopic expression of miR­486 significantly repressed the self­renewal and invasion of CSCs in vitro and tumorigenesis in vivo. Notably, we found that sirtuin 1 (Sirt1) served as a direct target of miR­486. The high expression of Sirt1 was involved in maintaining the self­renewal and tumorigenic potential of liver CSCs. The results of the present study indicated that the miR­486­Sirt1 axis was involved in suppressing CSC traits and tumor progression.