Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers
The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3091 |
| _version_ | 1797550053910380544 |
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| author | Euna Jeong Yejin Lee Youngju Kim Jieun Lee Sukjoon Yoon |
| author_facet | Euna Jeong Yejin Lee Youngju Kim Jieun Lee Sukjoon Yoon |
| author_sort | Euna Jeong |
| collection | DOAJ |
| description | The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) for each of approximately 18,000 genes identified from mRNA and RNAi (i.e., shRNA and sgRNA) data from colon cancer cell lines. The predictivity score measures the difference in RNAi efficacy between cell lines with high vs. low expression of the target gene, while the descriptivity score measures the differential mRNA expression between groups of cell lines exhibiting high vs. low RNAi efficacy. The mRNA expression of 90 and 74 genes showed significant (<i>p</i> < 0.01) cross-association scores with the shRNA and sgRNA data, respectively. The genes were found to be from diverse molecular classes and have different functions. Cross-association scores for the mRNA expression of six genes (<i>CHAF1B, HNF1B, HTATSF1, IRS2, POLR2B</i> and <i>SATB2</i>) with both shRNA and sgRNA efficacy were significant. These genes were interconnected in cancer-related transcriptional networks. Additional experimental validation confirmed that siHNF1B efficacy is correlated with <i>HNF1B</i> mRNA expression levels in diverse colon cancer cell lines. Furthermore, <i>KIF26A</i> and <i>ZIC2</i> gene expression, with which shRNA efficacy displayed significant scores, were found to correlate with the survival rate from colon cancer patient data. This study demonstrates that bidirectional predictivity and descriptivity calculations between mRNA and RNAi data serve as useful resources for the discovery of predictive anticancer targets. |
| first_indexed | 2024-03-10T15:23:00Z |
| format | Article |
| id | doaj.art-c5f9ca07aba74011bba6652480e5cdb7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:23:00Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c5f9ca07aba74011bba6652480e5cdb72023-11-20T18:18:39ZengMDPI AGCancers2072-66942020-10-011211309110.3390/cancers12113091Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon CancersEuna Jeong0Yejin Lee1Youngju Kim2Jieun Lee3Sukjoon Yoon4Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaResearch Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, KoreaThe availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) for each of approximately 18,000 genes identified from mRNA and RNAi (i.e., shRNA and sgRNA) data from colon cancer cell lines. The predictivity score measures the difference in RNAi efficacy between cell lines with high vs. low expression of the target gene, while the descriptivity score measures the differential mRNA expression between groups of cell lines exhibiting high vs. low RNAi efficacy. The mRNA expression of 90 and 74 genes showed significant (<i>p</i> < 0.01) cross-association scores with the shRNA and sgRNA data, respectively. The genes were found to be from diverse molecular classes and have different functions. Cross-association scores for the mRNA expression of six genes (<i>CHAF1B, HNF1B, HTATSF1, IRS2, POLR2B</i> and <i>SATB2</i>) with both shRNA and sgRNA efficacy were significant. These genes were interconnected in cancer-related transcriptional networks. Additional experimental validation confirmed that siHNF1B efficacy is correlated with <i>HNF1B</i> mRNA expression levels in diverse colon cancer cell lines. Furthermore, <i>KIF26A</i> and <i>ZIC2</i> gene expression, with which shRNA efficacy displayed significant scores, were found to correlate with the survival rate from colon cancer patient data. This study demonstrates that bidirectional predictivity and descriptivity calculations between mRNA and RNAi data serve as useful resources for the discovery of predictive anticancer targets.https://www.mdpi.com/2072-6694/12/11/3091gene expressionshRNA screeningCRISPRanticancer targetsbiomarkersprecision medicine |
| spellingShingle | Euna Jeong Yejin Lee Youngju Kim Jieun Lee Sukjoon Yoon Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers Cancers gene expression shRNA screening CRISPR anticancer targets biomarkers precision medicine |
| title | Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers |
| title_full | Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers |
| title_fullStr | Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers |
| title_full_unstemmed | Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers |
| title_short | Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers |
| title_sort | analysis of cross association between mrna expression and rnai efficacy for predictive target discovery in colon cancers |
| topic | gene expression shRNA screening CRISPR anticancer targets biomarkers precision medicine |
| url | https://www.mdpi.com/2072-6694/12/11/3091 |
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