Department of Integrated Traditional & Western Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Intensive Care Unit, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Phytomedicine. 2022 Sep;104:154299. doi: 10.1016/j.phymed.2022.154299. Epub 2022 Jun 27.
N-methyladenosine (mA) has been identified to regulate the tumorigenesis and development of various tumors, including non-small cell lung cancer (NSCLC). Isoliquiritigenin (ISL), derived from the Chinese herb licorice, shows a significant anti-tumor activity on multiple human cancers. However, the role of ISL on NSCLC through mA is still unclear.
Here, we investigated the anti-tumor effect of ISL on NSCLC, and explored whether ISL affected the NSCLC phenotype by modulating its mA modification.
Cell proliferation, migration and invasion assays were performed to evaluate the inhibitory effects of ISL on NSCLC cells. MA enrichment was determined by mA quantitative analysis. The mechanism regarding IGF2BP3 was explored using RIP-PCR, MeRIP-qPCR and RNA decay analysis.
ISL significantly repressed the proliferation, migration and invasion of NSCLC cells in vitro. In addition, mA reader IGF2BP3 expression significantly increased in NSCLC tissues compared to adjacent tissues, and was positively correlated with NSCLC patients' poor survival. Mechanistically, ISL reduced mA modification and down-regulated IGF2BP3 expression in NSCLC. Furthermore, IGF2BP3 enhanced the mRNA stability of twist family bHLH transcription factor 1 (TWIST1) in mA-dependent manner. Moreover, ISL treatment combined with TWSIT1 knockdown effectively reversed IGF2BP3 overexpression-induced NSCLC cells' proliferation, migration and invasion.
Our findings uncover that ISL might function as an anticarcinogen through targeting IGF2BP3/mA/TWIST1 axis for NSCLC.
N6-甲基腺苷（m6A）已被鉴定可调节多种肿瘤的发生和发展，包括非小细胞肺癌（NSCLC）。甘草中的异甘草素（ISL）对多种人类癌症表现出显著的抗肿瘤活性。然而，ISL 通过 mA 对 NSCLC 的作用尚不清楚。
本研究旨在探讨 ISL 对 NSCLC 的抗肿瘤作用，并探讨 ISL 是否通过调节其 mA 修饰来影响 NSCLC 表型。
采用细胞增殖、迁移和侵袭实验评估 ISL 对 NSCLC 细胞的抑制作用。通过 mA 定量分析测定 mA 富集。使用 RIP-PCR、MeRIP-qPCR 和 RNA 衰变分析探索 IGF2BP3 的机制。
ISL 显著抑制 NSCLC 细胞在体外的增殖、迁移和侵袭。此外，与相邻组织相比，IGF2BP3 在 NSCLC 组织中的表达显著增加，并且与 NSCLC 患者的不良预后呈正相关。机制上，ISL 降低了 NSCLC 中的 mA 修饰和 IGF2BP3 表达。此外，IGF2BP3 以 mA 依赖性方式增强 TWIST 家族 bHLH 转录因子 1（TWIST1）的 mRNA 稳定性。此外，ISL 联合 TWIST1 敲低治疗可有效逆转 IGF2BP3 过表达诱导的 NSCLC 细胞增殖、迁移和侵袭。
我们的研究结果表明，ISL 可能通过靶向 IGF2BP3/mA/TWIST1 轴发挥抗癌作用，为 NSCLC 提供新的治疗策略。
