Background: 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.
Purpose: Here, we investigated the anti-tumor effect of ISL on NSCLC, and explored whether ISL affected the NSCLC phenotype by modulating its mA modification.
Methods: 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.
Results: 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.
Conclusion: Our findings uncover that ISL might function as an anticarcinogen through targeting IGF2BP3/mA/TWIST1 axis for NSCLC.
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Isoliquiritigenin inhibits non-small cell lung cancer progression via mA/IGF2BP3-dependent TWIST1 mRNA stabilization.
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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. Electronic address:
Background: 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.
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1. Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone structure 4,2',4'-trihydroxychalcone. In the present study, we report, for the first time, ISL-induced inhibition of the proliferation of the human non-small cell lung cancer A549 cell line.
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