Interplay between the RNA binding‐protein Musashi and developmental signaling pathways

Abstract

Musashi comprises an evolutionarily conserved family of RNA-binding proteins (RBP) that regulate cell fate decisions during embryonic development and play key roles in the maintenance of self-renewal and differentiation of stem cells and adult tissues.More recently, several studies have shown that any dysregulation of MSI1 and MSI2can lead to cellular dysfunctions promoting tissue instability and tumorigenesis.Moreover, several reports have characterized many molecular interactions between members of the Musashi family with ligands and receptors of the signaling pathways responsible for controlling normal embryonic development: Notch, Transforming Growth Factor Beta (TGF-β), Wingless (Wnt) and Hedgehog Signaling (Hh); all of which, when altered, are strongly associated with cancer onset and progression, especially in pediatric tumors. In this context, the present review aims to compile possible cross-talks between Musashi proteins and members of the above cited molecular pathways for which dysregulation plays important roles during carcinogenesis and may be modulated by these RBP. K E Y W O R D S cancer, Musashi

MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune‐related pathways

“…These characteristics demand urgent identification of predictive biomarkers of prognosis to guide and improve clinical management 5 . Given that aberrant expression of RBPs has been implicated in cancer development, and because RBPs have been recognized as biomarkers of prognosis and potential therapeutic targets, here we explored the role of MSI2 expression and its clinical implications in ACC pathobiology 7,8 …”

“…Recently, several studies have shown that dysregulated expression and activity of RNA‐binding proteins (RBPs) as posttranscriptional regulators are associated with initiation, progression, and chemoresistance of various types of tumors 6–8 . The RBP Musashi‐2 (MSI2) has recently been recognized as a potential prognostic biomarker or a therapeutic target, or both, in many cancers, including hematopoietic malignancies and solid tumors 6,8 . Elevated expression of MSI2 plays important roles in malignant transformation, tumor proliferation, cell cycle, migration, invasion, epithelial‐mesenchymal transition (EMT), and autophagy 9–16 .…”

“…[6][7][8] The RBP Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker or a therapeutic target, or both, in many cancers, including hematopoietic malignancies and solid tumors. 6,8 Elevated expression of MSI2 plays important roles in malignant transformation, tumor proliferation, cell cycle, migration, invasion, epithelial-mesenchymal transition (EMT), and autophagy. [9][10][11][12][13][14][15][16] However, MSI2 expression and its clinical significance in ACC remain unclear.…”

MiMIC analysis reveals an isoform specific role forDrosophilaMusashi in follicle stem cell maintenance and escort cell function

“…In the intestinal epithelium, a requirement for vertebrate Msi proteins in maintaining quiescent intestinal stem cells has been demonstrated (Yousefi et al, 2016). Interestingly, vertebrate Musashi proteins have been shown to interact with the Notch, Transforming Growth Factor Beta (TGF-ß), Wnt and Hh signalling pathways in differing contexts (reviewed in (das Chagas, Baroni, Brassesco, & Tone, 2020)). Here we describe a specific context where Drosophila Msi is required for epithelial stem cell homeostasis and demonstrate an interaction between Msi and the Wnt signalling pathway.…”

The Fine Art of Writing a Message: RNA Metabolism in the Shaping and Remodeling of the Nervous System

“…In the absence of murine msi1 , the differentiation potential of neuronal precursors is lost (Sakakibara et al, 2002 ). In vitro studies showed that during cell differentiation, Msi1 modulates the Notch pathway by binding to the 3′UTR of numb mRNA, which results in inhibition of numb mRNA translation and thereby an increase in Notch signaling (Imai et al, 2001 ; Berdnik et al, 2002 ; das Chagas et al, 2020 ). Based on information collected from mammalian model systems, the mechanism proposed for this type of inhibition is mediated by Msi1 physically interacting with the Poly(A) binding protein (PABP), both bound to numb mRNA (Kawahara et al, 2008 ).…”