Department of Respiratory and Critical Care Medicine, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, Jiangsu 225300, China.
Cell Mol Biol (Noisy-le-grand). 2024 Jun 5;70(6):108-113. doi: 10.14715/cmb/2024.70.6.17.
Oridonin belongs to a small molecule from the Chinese herb Rabdosia rubescens with potent anticancer activity. In spite of the lncRNA AFAP1-AS1 has been proven to exert promoting function in lung cancer, its relationship with oridonin in lung cancer is obscure. Therefore, our study planned to explore the potential of oridonin in lung cancer as well as unveil the regulatory mechanism of oridonin on AFAP1-AS1 in lung cancer cells. In the present study, oridonin inhibited lung cancer cell proliferation, migration, as well as invasion, as evidenced by MTT, wound healing, as well as transwell assays. Besides, we observed that oridonin could downregulate AFAP1-AS1 expression, and overexpressed AFAP1-AS1 could reverse the repressive effects of oridonin on lung cancer cell proliferation, migration, as well as invasion. More importantly, we found that AFAP1-AS1 could bind to IGF2BP1 through starBase prediction and RIP assay. The expression level of IGF2BP1 was also reduced by oridonin treatment but reversed after AFAP1-AS1 overexpression. Additionally, we proved that overexpressed IGF2BP1 could reverse the repressive impacts of oridonin on lung cancer cell proliferation, migration, as well as invasion. Further, in vivo experiments validated the repressive role of oridonin on tumor growth of lung cancer. Together, oridonin inhibits lung cancer cell proliferation as well as migration by modulating AFAP1-AS1/IGF2BP1, and AFAP1-AS1/IGF2BP1 possesses the potential to be a promising therapy targeting for lung cancer, especially in oridonin treatment.
冬凌草甲素是一种来源于中国草药冬凌草的小分子，具有很强的抗癌活性。尽管 lncRNA AFAP1-AS1 已被证明在肺癌中发挥促进作用，但它与冬凌草甲素在肺癌中的关系尚不清楚。因此，我们的研究计划探讨冬凌草甲素在肺癌中的潜力，并揭示冬凌草甲素对肺癌细胞中 AFAP1-AS1 的调控机制。在本研究中，冬凌草甲素抑制肺癌细胞增殖、迁移和侵袭，MTT、划痕愈合和 Transwell 实验结果均证实了这一点。此外，我们观察到冬凌草甲素可以下调 AFAP1-AS1 的表达，而过表达 AFAP1-AS1 可以逆转冬凌草甲素对肺癌细胞增殖、迁移和侵袭的抑制作用。更重要的是，我们通过 starBase 预测和 RIP 实验发现 AFAP1-AS1 可以与 IGF2BP1 结合。IGF2BP1 的表达水平也被冬凌草甲素处理所降低，但在 AFAP1-AS1 过表达后被逆转。此外，我们证明过表达 IGF2BP1 可以逆转冬凌草甲素对肺癌细胞增殖、迁移和侵袭的抑制作用。此外，体内实验验证了冬凌草甲素对肺癌肿瘤生长的抑制作用。综上所述，冬凌草甲素通过调节 AFAP1-AS1/IGF2BP1 抑制肺癌细胞增殖和迁移，AFAP1-AS1/IGF2BP1 具有成为治疗肺癌的有前途的靶点的潜力，特别是在冬凌草甲素治疗中。
