Tanshindiol C inhibits proliferation and induces apoptosis in non-small cell lung cancer by modulating miR-491-3p expression

Background: Tanshindiol C (TanC) has been validated to repress proliferation in several cancer cell types. However, the underlying molecular mechanism of TanC on non-small cell lung cancer (NSCLC) cell proliferation and apoptosis is unclear. The aim of the present study was to explore whether microRNAs (miRNAs) and downstream target were involved in TanC-induced NSCLC cell death in vitro. Methods: miRNAs expression profiling was analyzed in A549 cells with or without TanC treatment using miRNAs microarray. Cell viability and apoptosis were detected using CCK8 and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexinv-FITC) double staining, respectively. Bioinformatics algorithms and luciferase reporter assay were performed to verify c-MYC as a direct target of miR-491-3p. Results: TanC showed an anti-proliferative and pro-apoptotic activity in A549 and H358 cells. We also found that an increase in miR-491-3p and a decrease in c-MYC expression levels were observed in TanC-stimulated A549 and H358 cells. c-MYC was a direct target of miR-491-3p, and overexpression of miR-491-3p repressed c-MYC protein expression by directly binding with the 3'-UTR of c-MYC. miR-491-3p mimics induced growth inhibition and apoptosis were abolished by the overexpression of c-MYC in A549 and 11358 cells. Conclusion: TanC had an effective ability to inhibit proliferation and induce apoptosis in NSCLC cells, and the underlying mechanism was mediated, at least partially, by regulating miR-491-3p/c-MYC signaling pathway.