A comprehensive expression landscape of RNA-binding proteins (RBPs) across 16 human cancer types

RNA-binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression in human cancer has not been well elucidated. Here, we bui...

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Bibliographic Details
Published inRNA biology Vol. 17; no. 2; pp. 211 - 226
Main Authors Zhang, Bin, Babu, Kamesh R., Lim, Chun You, Kwok, Zhi Hao, Li, Jia, Zhou, Siqin, Yang, Henry, Tay, Yvonne
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.02.2020
Subjects
cancer
Expression landscape
Research Paper
RNA binding protein
cancer
Expression landscape
RNA binding protein
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Summary:RNA-binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression in human cancer has not been well elucidated. Here, we built a comprehensive expression landscape of 1504 RBPs across 16 human cancer types, which revealed that RBPs are predominantly upregulated in tumours and this phenomenon is affected by the tumour immune subtypes and microenvironment. Across different cancer types, 109 RBPs are consistently upregulated while 41 RBPs are consistently downregulated. These up-regulated and down-regulated RBPs show distinct molecular characteristics and prognostic effects, whereas their dysregulation is mediated by distinct cis/trans-regulatory mechanisms. Finally, we validated one candidate PABPC1L that might promote colon tumorigenesis by regulating mRNA splicing. In summary, we built a comprehensive expression landscape of RBPs across different cancer types and identified consistently dysregulated RBPs which could be novel targets for developing broad-spectrum anticancer agents.
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Author Summary
To explore the potential role of RBPs in cancer development, somatic mutation landscape of splicing factors across 33 human cancer types, and mutation landscape of RBPs across 26 cancer types have been established recently. However, the expression landscape of RBPs across different human cancer types is still under debate. Kechavarzi showed that RBPs are overrepresented in top quantile upregulated genes, while Wang et al claimed that RBPs are predominantly downregulated in tumours comparing to the adjacent normal tissue across 15 human cancer types only using TCGA data. Here we provide much stronger evidence supporting that RBPs are preferentially upregulated in tumours. We also further identified 109 RBPs are consistently upregulated while 41 RBPs are consistently downregulated across different cancer types. By integrated analysis of somatic copy number alteration, DNA methylation and TF/miRNA-RBP interactome, we found that upregulation and downregulation of RBPs have distinct molecular mechanisms. Finally, we validated one RBP PABPC1L that might promote colon tumorigenesis by regulating mRNA splicing.
ISSN:1547-6286
1555-8584
DOI:10.1080/15476286.2019.1673657