Abstract
Lung cancer is one of the most fatal malignancies and the leading cause of cancer death worldwide. β-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 β-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 β-elemene on lung cancer. Firstly, outcomes suggested that β-elemene restrained the malignant behaviors of A549 together with H1299 cells. Thereafter, we observed that β-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 β-elemene. Mechanistically, β-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. More importantly, β-elemene contributed to the augmented PTEN expression via suppressing its m6A modification. To sum up, we provided strong clues that β-elemene promoted PTEN expression to retard lung cancer progression by the regulation of METTL3-mediated m6A modification.
Highlights
Lung cancer is one of the most prevailing malignant tumors around the world, and its morbidity and mortality rank first among all the cancers [1, 2]
Lung cancer seriously endangers human life and aggravates the global public health burden [3]. e deaths from lung cancer are approximately 1.8 million in 2018, and it is estimated that the number of cases succumbed to lung cancer will rise to 3 million by 2035 worldwide [4, 5]. e therapeutic interventions for lung cancer mainly consist of surgical resection, radiotherapy, chemotherapy, and gene-targeted therapy, and surgery resection is a radical therapy in the absence of metastasis [6, 7]. e overall 5-year survival rate is still stagnant at about 15% in spite of tremendous advance in techniques and therapeutic methods [8]
The results indicated that β-elemene promoted the apoptosis of lung cancer tissue, whereas overexpressing METTL3 reversed the effected induced by β-elemene (Figures 5(e) and 5(f ). β-Elemene increased the expression of Bax and caspase 3, but downregulated the expression of Bcl-2
Summary
Lung cancer is one of the most prevailing malignant tumors around the world, and its morbidity and mortality rank first among all the cancers [1, 2]. Journal of Oncology from Curcuma zedoaria, has been proven to be a noncytotoxic anticancer agent in a wide range of malignancies, such as renal cell carcinoma, breast cancer, glioma, and gastric cancer [13,14,15,16]. There has been increasing interest in seeking potential function and regulatory mechanism of β-elemene in human cancer. Β-elemene has been demonstrated to present anticancer impacts on the development of lung cancer [20], more specific mechanisms are largely to be further expounded. E purpose of this study is to validate the function of β-elemene in cell expansion and apoptosis of lung cancer and elucidate its molecular mechanism, which provides novel insights into the potential role of m6A modification in the impacts of β-elemene on lung cancer
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