beta-Elemene Restrains PTEN mRNA Degradation to Restrain the Growth of Lung Cancer Cells via METTL3-Mediated N-6 Methyladenosine Modification

Lung cancer is one of the most fatal malignancies and the leading cause of cancer death worldwide. beta-Elemene, a well-known anticancer drug, has drawn a great deal of attention from researchers attributed to its limited side impacts. N-6-Methyladenosine (m(6)A) modification is the most common RNA modification and plays a vital role in the pathogenesis of multiple tumors. However, the functional link between beta-elemene and the m(6)A modification in lung cancer development remains unexplored. In this study, we investigated whether m(6)A modification was responsible for the impacts of beta-elemene on lung cancer. Firstly, outcomes suggested that beta-elemene restrained the malignant behaviors of A549 together with H1299 cells. Thereafter, we observed that beta-elemene markedly regulated METTL3, YTHDF1, and YTHDC1 among various m(6)A modulators. METTL3 was selected for further study because of its oncogenic function in lung cancer. RT-qRCR and western blot assays exhibited that the mRNA and protein expression levels of METTL3 were lessened by the administration of beta-elemene. Mechanistically, beta-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. More importantly, beta-elemene contributed to the augmented PTEN expression via suppressing its m(6)A modification. To sum up, we provided strong clues that beta-elemene promoted PTEN expression to retard lung cancer progression by the regulation of METTL3-mediated m(6)A modification.