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Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.

ABSTRACT: RNA-binding proteins (RBPs) play a critical role in the regulation of various RNA processes, including splicing, cleavage and polyadenylation, transport, translation and degradation of coding RNAs, non-coding RNAs and microRNAs. Recent studies indicate that RBPs not only play an instrumental role in normal cellular processes but have also emerged as major players in the development and spread of cancer. Herein, we review the current knowledge about RNA binding proteins and their role in tumorigenesis as well as the potential to target RBPs for cancer therapeutics.

SUBMITTER: Mohibi S

PROVIDER: S-EPMC6848768 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.

Mohibi Shakur S Chen Xinbin X Zhang Jin J

Pharmacology & therapeutics 20190711

RNA-binding proteins (RBPs) play a critical role in the regulation of various RNA processes, including splicing, cleavage and polyadenylation, transport, translation and degradation of coding RNAs, non-coding RNAs and microRNAs. Recent studies indicate that RBPs not only play an instrumental role in normal cellular processes but have also emerged as major players in the development and spread of cancer. Herein, we review the current knowledge about RNA binding proteins and their role in tumorige ...[more]

PMID: 31302171

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Project description:Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. Although much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act posttranscriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBP) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance. Following identification of Musashi as a regulator of progenitor cell identity in Drosophila, the human Musashi proteins were initially linked to control of maintenance of hematopoietic stem cells, then stem cell compartments for additional cell types. More recently, the Musashi proteins were found to be overexpressed and prognostic of outcome in numerous cancer types, including colorectal, lung, and pancreatic cancers; glioblastoma; and several leukemias. MSI1 and MSI2 bind and regulate the mRNA stability and translation of proteins operating in essential oncogenic signaling pathways, including NUMB/Notch, PTEN/mTOR, TGFβ/SMAD3, MYC, cMET, and others. On the basis of these activities, MSI proteins maintain cancer stem cell populations and regulate cancer invasion, metastasis, and development of more aggressive cancer phenotypes, including drug resistance. Although RBPs are viewed as difficult therapeutic targets, initial efforts to develop MSI-specific inhibitors are promising, and RNA interference-based approaches to inhibiting these proteins have had promising outcomes in preclinical studies. In the interim, understanding the function of these translational regulators may yield insight into the relationship between mRNA expression and protein expression in tumors, guiding tumor-profiling analysis. This review provides a current overview of Musashi as a cancer driver and novel therapeutic target. Clin Cancer Res; 23(9); 2143-53. ©2017 AACR.

Dataset Information

Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.

Publications

Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.

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