Feng Yuxu, Li Chenchen, Liu Siwen, Yan Fei, Teng Yue, Li Xiaoyou, Sun Yan
Department of Orthopaedics, Pukou Central Hospital, Pukou Branch Hospital of Jiangsu Province Hospital, Nanjing, Jiangsu, China.
Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
J Oncol. 2022 Jan 12;2022:3472745. doi: 10.1155/2022/3472745. eCollection 2022.
Lung cancer is one of the most fatal malignancies and the leading cause of cancer death worldwide. -Elemene, a well-known anticancer drug, has drawn a great deal of attention from researchers attributed to its limited side impacts. N-Methyladenosine (mA) modification is the most common RNA modification and plays a vital role in the pathogenesis of multiple tumors. However, the functional link between -elemene and the mA modification in lung cancer development remains unexplored. In this study, we investigated whether mA modification was responsible for the impacts of -elemene on lung cancer. Firstly, outcomes suggested that -elemene restrained the malignant behaviors of A549 together with H1299 cells. Thereafter, we observed that -elemene markedly regulated METTL3, YTHDF1, and YTHDC1 among various mA 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 -elemene. Mechanistically, -elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. More importantly, -elemene contributed to the augmented PTEN expression via suppressing its mA modification. To sum up, we provided strong clues that -elemene promoted PTEN expression to retard lung cancer progression by the regulation of METTL3-mediated mA modification.
肺癌是最致命的恶性肿瘤之一，也是全球癌症死亡的主要原因。榄香烯是一种著名的抗癌药物，因其副作用有限而备受研究人员关注。N-甲基腺苷（mA）修饰是最常见的RNA修饰，在多种肿瘤的发病机制中起着至关重要的作用。然而，榄香烯与肺癌发生发展中mA修饰之间的功能联系仍未被探索。在本研究中，我们调查了mA修饰是否介导了榄香烯对肺癌的影响。首先，结果表明榄香烯抑制了A549和H1299细胞的恶性行为。此后，我们观察到在各种mA调节剂中，榄香烯显著调节了METTL3、YTHDF1和YTHDC1。由于METTL3在肺癌中的致癌作用，我们选择对其进行进一步研究。RT-qRCR和蛋白质印迹分析表明，榄香烯给药后METTL3的mRNA和蛋白质表达水平降低。机制上，榄香烯通过靶向METTL3在体内和体外对肺癌细胞生长产生抑制作用。更重要的是，榄香烯通过抑制PTEN的mA修饰促进了PTEN的表达。综上所述，我们提供了有力线索，表明榄香烯通过调节METTL3介导的mA修饰促进PTEN表达，从而延缓肺癌进展。
