Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 May 18

PMID 27186987

Citations 1

Authors

Atefeh Lafzi

Hilal Kazan

Affiliations

Soon will be listed here.

Abstract

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs. As a case study, we applied our model to Lung squamous cell carcinoma (LUSC) data as we found that there are several RBPs differentially expressed in LUSC. Including RBP-mediated regulatory effects in addition to the other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure that accounts for the adaptive search employed by lasso regularization, we identified the candidate regulators in LUSC. Remarkably, several of these candidate regulators are RBPs. Furthermore, majority of the candidate regulators have been previously found to be associated with lung cancer. To investigate the mechanisms that are controlled by these regulators, we predicted their target gene sets based on our model. We validated the target gene sets by comparing against experimentally verified targets. Our results suggest that the future studies of gene expression in cancer must consider the effect of RBP-mediated regulation.

Citing Articles

Differential expression of RNA-binding proteins in bronchial epithelium of stable COPD patients.

Ricciardi L, Dal Col J, Casolari P, Memoli D, Conti V, Vatrella A Int J Chron Obstruct Pulmon Dis. 2018; 13:3173-3190.

PMID: 30349226 PMC: 6190813. DOI: 10.2147/COPD.S166284.

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