Abstract
Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality among all carcinomas. However, it is difficult to diagnose in the early stage, and current therapeutic efficacy is not ideal. Although numerous studies have revealed that Ailanthone (Aila), a natural product, can inhibit multiple cancers by reducing cell proliferation and invasion and inducing apoptosis, the mechanism by which Aila represses NSCLC progression in a time-dependent manner remains unclear. In this study, we observed that most long noncoding RNAs (lncRNAs) were either notably up- or downregulated in NSCLC cells after treatment with Aila. Moreover, alterations in lncRNA expression induced by Aila were crucial for the initiation and metastasis of NSCLC. Furthermore, in our research, expression of DUXAP8 was significantly downregulated in NSCLC cells after treatment with Aila and regulated expression levels of EGR1. In conclusion, our findings demonstrate that Aila is a potent natural suppressor of NSCLC by modulating expression of DUXAP8 and EGR1.
Highlights
Lung cancer is the most widespread malignant tumor and has the highest mortality among all cancers
The results showed that overexpressing Double homeobox A pseudogene 8 (DUXAP8) after Aila treatment can reduce the apoptosis (Figure 8A), indicating that DUXAP8 may play an important role during the cell apoptosis
The results revealed that after knockdown of DUXAP8, expression of early growth response factor-1 (EGR1) was much higher than in the control group by both RT-PCR and western blot analysis; in contrast, expression levels of EGR1 were significantly decreased in the overexpression group (Figures 8F, H)
Summary
Lung cancer is the most widespread malignant tumor and has the highest mortality among all cancers. Based on one global cancer study conducted by the International Agency for Research on Cancer (IARC), there were approximately 4 million newly diagnosed and dead lung cancer patients in 2018 worldwide [1]. The number of people who are initially diagnosed with lung cancer is approximately 770,000, and those who die from lung cancer is nearly 700,000 annually in China [2]. All of these data indicate that lung cancer is a tremendous threat to public health. Lung cancer is classified into a variety of histological subtypes, among which NSCLC accounts for approximately 80-85% of all cases [3, 4]. Due to the insidious onset of NSCLC, the majority of patients
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