RNA Biology: Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells
Caihong Yi, Guiming Li, Dmitri N Ivanov, Zhonghua Wang, Mitzli X Velasco, Greco Hernández, Soni Kaundal, Johanna Villarreal, Yogesh K Gupta, Mei Qiao, Christopher G Hubert, Matthew J Hart, Luiz OF Penalva
RNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting as a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high in GBMs and other tumor types and correlate with poor clinical outcome. Moreover, Msi1 has been implicated in chemo- and radio-resistance. Msi1 modulates a range of cancer-relevant processes and pathways and regulates the expression of stem cell markers and oncogenic factors via mRNA translation/stability. To identify Msi1 inhibitors capable of blocking its RNA binding function, we performed a ~ 25,000 compound fluorescence polarization screen. NMR and LSPR were used to confirm the direct interaction between Msi1 and luteolin, the leading compound. Luteolin displayed strong interaction with Msi1 RNA binding domain 1 (RBD1). As …
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