Available online 8 March 2024

β-elemene inactivates the MAPK4/mTOR pathway and stimulates autophagy in NSCLC cells.

β-elemene silences MAPK4 which could inhibit autophagy in NSCLCs by activating miR-127-3p.

β-elemene enables pre-miR-127 to escape from nucleoplasmic translocation restrictions and mature towards miR-127-3p by inhibiting CBX8.

β-elemene has been observed to exert inhibitory effects on a multitude of tumors, primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis. The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the therapeutic intervention of non-small cell lung cancer (NSCLC). Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs. Our findings indicate that β-elemene facilitates the maturation of miR-127-3p by inhibiting CBX8. Functioning as an upstream regulator of MAPK4, miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4, thereby inducing autophagy in NSCLCs. Additionally, β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP. Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4. Taken together, the detailed understanding of the mechanisms through which β-elemene induces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.

β-elemene

miR-127-3p

NSCLC

Akt/mTOR/p70S6K

MAPK4

© 2024 Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.