Open AccessSuppression of Musashi‑2 by the small compound largazole exerts inhibitory effects on malignant cells
Author(s) -
Min Wang,
Xiaoyan Sun,
Yunyun Zhou,
Kuojun Zhang,
Yongzhi Lu,
Jinsong Liu,
Yunchao Huang,
Guizhen Wang,
Sheng Jiang,
GuangBiao Zhou
Publication year - 2020
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2020.4993
Subject(s) - biology , oncogene , cancer research , downregulation and upregulation , cell cycle , apoptosis , myeloid leukemia , regulator , cancer , molecular medicine , cancer cell , lung cancer , pharmacology , medicine , gene , biochemistry , genetics
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.