RNA-binding protein Musashi homolog 1 (MSI1) (MSI1)

RNA-binding protein Musashi homolog 1 (MSI1) is a highly conserved protein that functions as a key post-transcriptional regulator of gene expression, primarily by repressing the translation of target mRNAs (UniProt O43347; Wikipedia). It is a well-established marker for neural stem cells and plays a critical role in maintaining the balance between stem cell self-renewal and differentiation (Kudinov et al., Clin Cancer Res 2017). In various malignancies, including glioblastoma, medulloblastoma, and colorectal cancer, MSI1 is frequently overexpressed and acts as an oncoprotein by repressing the translation of tumor suppressors such as Numb, p21, and APC (Lan et al., Mol Oncol 2015). This repression leads to the constitutive activation of oncogenic signaling pathways, most notably the Notch and Wnt pathways, which drive tumor growth, metastasis, and chemoresistance (Kudinov et al., Clin Cancer Res 2017; Lan et al., Mol Oncol 2015). Consequently, MSI1 is considered a promising therapeutic target, with research focusing on small molecule inhibitors like (-)-gossypol and luteolin that disrupt its ability to bind RNA (Clingman et al., eLife 2014; Yi et al., RNA Biol 2018). However, the development of MSI1-targeted therapies faces challenges due to the protein's role in normal stem cell maintenance and the inherent difficulty of drugging RNA-binding proteins (Kudinov et al., Clin Cancer Res 2017).

Other names

Musashi-1Musashi homolog 1MSI1musashi RNA binding protein 1

Inhibition of RNA binding to target transcripts (e.g., Numb, p21, APC) (Lan et al., Mol Oncol 2015); Allosteric inhibition of the RNA recognition motif (RRM) (Clingman et al., eLife 2014).