MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. They are involved in almost all cellular processes, and many have been described as potential oncogenes or tumor suppressors. MicroRNA-373 (miR-373), which was first identified as a human embryonic stem cell (ESC)-specific miRNA, is suggested to be implicated in the regulation of cell proliferation, apoptosis, senescence, migration and invasion, as well as DNA damage repair following hypoxia stress. Deregulation of miR-373 has been demonstrated in a number of cancers, whether it acts as an oncogene or a tumor suppressor, however, seems to be context dependent. In this review, we focus on the diverse functions of miR-373 and its implication in cancers.

Gastric cancer (GC) is a common type of malignancy worldwide, and chemotherapeutic resistance accounts for the majority of the failures in clinical treatment. MicroRNAs (miRs) are a class of small non-coding RNAs, which serve essential roles in GC. The present study aimed to investigate the potential role of miR-25 in the cisplatin sensitivity of GC cells. The expression level of miR-25 was significantly upregulated in the cisplatin-resistant GC cell line SGC-7901/DDP compared with the SGC-7901 parental cell line. Overexpression of miR-25 significantly enhanced cell cycle progression and decreased the sensitivity of SGC-7901 cells to cisplatin, whereas inhibition of miR-25 in the SGC-7901/DDP cisplatin-resistant cells resulted in cell cycle arrest at the G/G phase and significantly increased drug sensitivity. Furthermore, the tumor suppressor forkhead box O3a (FOXO3a) was identified as a direct target gene of miR-25 by luciferase assay and western blot analysis, and was shown to mediate the drug-resistance phenotype of GC cells. These findings suggest that upregulation of miR-25 is important for GC cells to establish a cisplatin-resistant phenotype via a FOXO3a-dependent mechanism. Therefore, targeting miR-25 may be a promising therapeutic approach to treat patients with cisplatin-resistant GC.

The anti-cancer activities of antibiotic anisomycin have been demonstrated in kidney, colon and ovarian cancers whereas its underlying mechanisms are not well elucidated. In this work, we investigated whether anisomycin is effective in sensitizes osteosarcoma cell response to chemotherapy. We show that anisomycin inhibits proliferation via inducing osteosarcoma cell arrest at G2/M phase, accompanied by the increased levels of mitotic marker cyclin B and the decreased levels of Rb and E2F-1. Anisomycin also induces apoptosis in a caspase-dependent manner in osteosarcoma cells. Importantly, anisomycin is less effective in normal control NIH3T3 cells compared to osteosarcoma cells. In addition, anisomycin inhibits osteosarcoma growth in xenograft mouse model and enhances the inhibitory effects of doxorubicin in osteosarcoma in vitro and in vivo. Mechanistically, anisomycin targets mitochondrial biogenesis in osteosarcoma as shown by the decreased mitochondrial membrane potential, suppressed mitochondrial respiration via decreasing complex I activity, reduced ATP production. Furthermore, mitochondrial biogenesis stimulator acetyl-L-Carnitine (ALCAR) significantly rescues the inhibitory effects of anisomycin in osteosarcoma cells. Our work demonstrates that anisomycin is active against osteosarcoma cells and the molecular mechanism of its action is the inhibition of mitochondrial biogenesis.