Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma.
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4871487?pdf=render |
| _version_ | 1819038587340980224 |
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| author | Atefeh Lafzi Hilal Kazan |
| author_facet | Atefeh Lafzi Hilal Kazan |
| author_sort | Atefeh Lafzi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:39:41Z |
| format | Article |
| id | doaj.art-74a00ef49e5d4b90bb52d9a0e4dfc6c3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:39:41Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-74a00ef49e5d4b90bb52d9a0e4dfc6c32022-12-21T19:09:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015535410.1371/journal.pone.0155354Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma.Atefeh LafziHilal KazanRNA-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.http://europepmc.org/articles/PMC4871487?pdf=render |
| spellingShingle | Atefeh Lafzi Hilal Kazan Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. PLoS ONE |
| title | Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. |
| title_full | Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. |
| title_fullStr | Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. |
| title_full_unstemmed | Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. |
| title_short | Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma. |
| title_sort | inferring rbp mediated regulation in lung squamous cell carcinoma |
| url | http://europepmc.org/articles/PMC4871487?pdf=render |
| work_keys_str_mv | AT atefehlafzi inferringrbpmediatedregulationinlungsquamouscellcarcinoma AT hilalkazan inferringrbpmediatedregulationinlungsquamouscellcarcinoma |