RNA-Binding Proteins in Cancer: Old Players and New Actors

Pereira, Bruno; Billaud, Marc; Almeida, Raquel

doi:10.1016/j.trecan.2017.05.003

Cited by 605 publications

(537 citation statements)

References 232 publications

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“…RBPs play critical roles in cell differentiation and tissue development, and aberrant RBP function is implicated in a wide range of diseases, including neurodegenerative disorders and neuropathies, myopathies, autoimmune paraneoplastic syndromes, and cancer [3]. For mRNAs, the role of RBPs in modulating global changes in gene expression at both the RNA and protein level becomes particularly important under conditions where new gene transcription is repressed, such as during inflammation, cell stress, and in response to genomic damage [4][5][6]. Under these conditions, changes in gene expression have been shown to result, in part, from alterations in RBP activity [7].…”

Section: Introductionmentioning

confidence: 99%

“…Under these conditions, changes in gene expression have been shown to result, in part, from alterations in RBP activity [7]. Furthermore, mutations affecting the expression or function of specific RBPs have been implicated in a variety of diseases, including cancer [3,6,8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, this finding has clear clinical relevance to the response of non-small cell lung cancers (NSCLCs) to chemotherapy in both mouse models and human patients, where the expression levels of two critical hnRNPA0 target RNAs, Gadd45α and p27, predicted the clinical response of mouse and human tumors to platinum therapy. Despite these types of data, and the recent surge of interest in the roles of RBPs in cancer chemosensitivity and resistance [6,14,29], general methods for the systematic identification and prioritization of RBPs that influence various biological responses, including the DDR in clinically relevant patient-based gene expression data sets, are lacking.…”

Section: Introductionmentioning

confidence: 99%

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Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

Krismer

Varmeh

Bird

et al. 2018

Preprint

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RNA-binding proteins (RBPs) play critical roles in regulating gene expression by modulating splicing, RNA stability, and protein translation. In response to various stimuli, alterations in RBP function contribute to global changes in gene expression, but identifying which specific RBPs are responsible for the observed changes in gene expression patterns remains an unmet need. Here, we present Transite a multipronged computational approach that systematically infers RBPs influencing gene expression changes through alterations in RNA stability and degradation. As a proof of principle, we applied Transite to public RNA expression data from human patients with non-small cell lung cancer whose tumors were sampled at diagnosis, or after recurrence following treatment with platinum-based chemotherapy. Transite implicated known RBP regulators of the DNA damage response and identified hnRNPC as a new modulator of chemotherapeutic resistance, which we subsequently validated experimentally. Transite serves as a generalizable framework for the identification of RBPs responsible for gene expression changes that drive cell-state transitions and adds additional value to the vast wealth of publicly-available gene expression data.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

Krismer

Varmeh

Bird

et al. 2018

Preprint

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“…interactions. RNA-binding proteins can recognize specific regulatory elements and modulate mRNA stability (2,3). MicroRNAs (miRs), a group of small noncoding RNAs of 21-24 nt length represent another important class of posttranscriptional regulators (4)(5)(6).…”

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confidence: 99%

miR‐574‐5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES‐1 induction

et al. 2019

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MicroRNAs (miRs) are important posttranscriptional regulators of gene expression. Besides their well‐characterized inhibitory effects on mRNA stability and translation, miRs can also activate gene expression. In this study, we identified a novel noncanonical function of miR‐574‐5p. We found that miR‐574‐5p acts as an RNA decoy to CUG RNA‐binding protein 1 (CUGBP1) and antagonizes its function. MiR‐574‐5p induces microsomal prostaglandin E synthase‐1 (mPGES‐1) expression by preventing CUGBP1 binding to its 3′UTR, leading to an enhanced alternative splicing and generation of an mPGES‐1 3′UTR isoform, increased mPGES‐1 protein expression, PGE2 formation, and tumor growth in vivo. miR‐574‐5p–induced tumor growth in mice could be completely inhibited with the mPGES‐1 inhibitor OIL Moreover, miR‐574‐5p is induced by IL‐1β and is strongly overexpressed in human nonsmall cell lung cancer where high mPGES‐1 expression correlates with a low survival rate. The discovered function of miR‐574‐5p as a CUGBP1 decoy opens up new therapeutic opportunities. It might serve as a stratification marker to select lung tumor patients who respond to the pharmacological inhibition of PGE2 formation.—Saul, M. J., Baumann, I., Bruno, A., Emmerich, A. C., Wellstein, J., Ottinger, S. M., Contursi, A., Dovizio, M., Donnini, S., Tacconelli, S., Raouf, J., Idborg, H., Stein, S., Korotkova, M., Savai, R., Terzuoli, E., Sala, G., Seeger, W., Jakobsson, P.‐J., Patrignani, P., Suess, B., Steinhilber, D. miR‐574‐5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES‐1 induction. FASEB J. 33, 6933–6947 (2019). http://www.fasebj.org

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“…[1][2][3] As essential functional proteins, RBPs were regarded as important components in the cellular regulation system, and their dysregulation can lead to the aberrant expression of downstream target genes. Such a complex biological phenomenon is associated with a multitude of highly dynamic underlying molecular events.…”

mentioning

confidence: 99%

Integrative analysis of significant RNA‐binding proteins in colorectal cancer metastasis

Zhou

Guo

2018

J of Cellular Biochemistry

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The aberrant expression of RNA-binding proteins (RBPs) plays a crucial role in the occurrence and progression of human cancer. However, the key functions of RBPs in the metastasis of colorectal cancer have not yet been fully elucidated. Here, we integrated multi-omics data and identified four differentially expressed RBPs (APOBEC3G, EEF1A2, EIF5AL1 and CELF3) in patients with colorectal cancer metastasis. To clarify the underlying molecular mechanisms, we systematically analyzed the genomic features and downstream regulatory relationships of the four RBPs. In a genomic level, the copy number variations of APOBEC3G, EEF1A2, and CELF3 demonstrated significantly differential distributions between metastatic and nonmetastatic patients. Besides that, combining sequence and expression information, we identified 436 putative RNA targets regulated by the four RBPs through strict multistep bioinformatics screening. For the downstream analysis, the evidence from functional enrichment analysis and public literature indicated the roles of these target genes in the carcinogenesis and progression of colorectal cancer. Furthermore, through the machine learning algorithm and statistical analysis, we obtained two gene candidates that had obvious effects on the metastasis and overall survival status of patients with colorectal cancer. In summary, our study comprehensively explored the influence of APOBEC3G, EEF1A2, EIF5AL1, and CELF3 in colorectal cancer metastasis, which may offer favorable perspectives for clinical diagnosis and therapy.

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RNA-Binding Proteins in Cancer: Old Players and New Actors

Cited by 605 publications

References 232 publications

Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

miR‐574‐5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES‐1 induction

Integrative analysis of significant RNA‐binding proteins in colorectal cancer metastasis

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