β-Elemene Restrains PTEN mRNA Degradation to Restrain the Growth of Lung Cancer Cells via METTL3-Mediated N6 Methyladenosine Modification

Abstract

Lung cancer is one of the most fatal malignancies and the leading cause of cancer death worldwide. <i>β</i>-Elemene, a well-known anticancer drug, has drawn a great deal of attention from researchers attributed to its limited side impacts. N⁶-Methyladenosine (m⁶A) modification is the most common RNA modification and plays a vital role in the pathogenesis of multiple tumors. However, the functional link between <i>β</i>-elemene and the m⁶A modification in lung cancer development remains unexplored. In this study, we investigated whether m⁶A modification was responsible for the impacts of <i>β</i>-elemene on lung cancer. Firstly, outcomes suggested that <i>β</i>-elemene restrained the malignant behaviors of A549 together with H1299 cells. Thereafter, we observed that <i>β</i>-elemene markedly regulated METTL3, YTHDF1, and YTHDC1 among various m⁶A 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 <i>β</i>-elemene. Mechanistically, <i>β</i>-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. More importantly, <i>β</i>-elemene contributed to the augmented PTEN expression via suppressing its m⁶A modification. To sum up, we provided strong clues that <i>β</i>-elemene promoted PTEN expression to retard lung cancer progression by the regulation of METTL3-mediated m⁶A modification.