Lycorine inhibited the cell growth of non-small cell lung cancer by modulating the miR-186/CDK1 axis.

Aims: Lycorine is a kind of natural alkaloid with anti-cancer potential. It has been demonstrated that lycorine processes high activity and specificity against the progression of cancers. However, the underlying molecular mechanisms by which lycorine regulates the formation and development of non-small cell lung cancer (NSCLC) remain largely unknown.
Main Methods: The effects of lycorine on the growth of NSCLC cells were determined by the cell counting kit-8 (CCK-8) assay, colony formation and flow cytometry analysis. RT-qPCR was performed to detect the expression of microRNA with lycorine treatment. The binding of miRNA and target genes was confirmed by luciferase reporter assay.
Key Findings: Lycorine significantly inhibited the proliferation and induced apoptosis of NSCLC cells. Mechanistically, lycorine up-regulated the expression of microRNA-186 in NSCLC cells. Depletion of miR-186 significantly reversed the suppressive effect of lycorine on the proliferation of NSCLC cells. Furthermore, the cyclin dependent kinase 1 (CDK1) was identified as one of the binding candidates of miR-186. Experimental analysis showed that miR-186 bound the 3'-untranslated region (3'-UTR) of CDK1 and suppressed the level of CDK1 in NSCLC cells. Consistently, exposure of lycorine significantly decreased the expression of CDK1. Restoration of CDK1 remarkably attenuated the inhibition of lycorine on the proliferation of NSCLC cells.
Significance: Our results uncovered the novel molecular mechanism of lycorine in suppressing the progression of NSCLC partially via regulating the miR-186/CDK1 axis.
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