Suppression of Musashi‑2 by the small compound largazole exerts inhibitory effects on malignant cells

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

doi:10.3892/ijo.2020.4993

Suppression of Musashi‑2 by the small compound largazole exerts inhibitory effects on malignant cells

Authors:
- Min Wang
- Xiao‑Yan Sun
- Yong‑Chun Zhou
- Kuo‑Jun Zhang
- Yong‑Zhi Lu
- Jinsong Liu
- Yun‑Chao Huang
- Gui‑Zhen Wang
- Sheng Jiang
- Guang‑Biao Zhou
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Affiliations: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China, Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650106, P.R. China, State Key Laboratory of Natural Medicines, and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China
Published online on: February 19, 2020 https://doi.org/10.3892/ijo.2020.4993
Pages: 1274-1283

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Abstract

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.

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