International journal of oncology · 2020
Suppression of Musashi‑2 by the small compound largazole exerts inhibitory effects on malignant cells.
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Wang Min, Sun Xiao-Yan, Zhou Yong-Chun, Zhang Kuo-Jun, Lu Yong-Zhi, Liu Jinsong, Huang Yun-Chao, Wang Gui-Zhen, Jiang Sheng, Zhou Guang-Biao
Аннотация
RNA‑binding protein Musashi‑2 (MSI2) serves as a regulator of numerous pivotal biological processes associated with cancer initiation, development and resistance to treatment, and may represent a promising drug target. However, whether MSI2 inhibition is of value in antitumor treatment remains to be determined. The present study demonstrated that MSI2 was upregulated in non‑small cell lung cancer (NSCLC) and was inversely associated with the clinical outcome of the patients. Molecular docking analysis demonstrated that the small compound largazole binds to and may be a potential inhibitor of MSI2. Largazole markedly decreased the protein and mRNA levels of MSI2 and suppressed its downstream mammalian target of rapamycin signaling pathway. Largazole also inhibited the proliferation and induced apoptosis of NSCLC and chronic myeloid leukemia (CML) cells (including bone marrow mononuclear cells harvested from CML patients). These results indicate that MSI2 is an emerging therapeutic target for NSCLC and CML, and the MSI2 inhibitor largazole may hold promise as a treatment for these malignancies.
Предметные рубрики MeSH
AdultAgedAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCell SurvivalDepsipeptidesFemaleGene Expression Regulation, NeoplasticHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLung NeoplasmsMaleMiceMiddle AgedModels, MolecularMolecular Docking SimulationProtein ConformationRNA-Binding ProteinsThiazolesUp-Regulation