Short tandem repeat mutations regulate gene expression in colorectal cancer
Abstract Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations i...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-53739-0 |
| _version_ | 1797274842414710784 |
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| author | Max A. Verbiest Oxana Lundström Feifei Xia Michael Baudis Tugce Bilgin Sonay Maria Anisimova |
| author_facet | Max A. Verbiest Oxana Lundström Feifei Xia Michael Baudis Tugce Bilgin Sonay Maria Anisimova |
| author_sort | Max A. Verbiest |
| collection | DOAJ |
| description | Abstract Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression data to study the gene regulatory effects of STR mutations in CRC. We confirm that STR mutability in CRC highly depends on the MSI status, repeat unit size, and repeat length. Furthermore, we present a set of 1244 putative expression STRs (eSTRs) for which the STR length is associated with gene expression levels in CRC tumours. The length of 73 eSTRs is associated with expression levels of cancer-related genes, nine of which are CRC-specific genes. We show that linear models describing eSTR-gene expression relationships allow for predictions of gene expression changes in response to eSTR mutations. Moreover, we found an increased mutability of eSTRs in MSI tumours. Our evidence of gene regulatory roles for eSTRs in CRC highlights a mostly overlooked way through which tumours may modulate their phenotypes. Future extensions of these findings could uncover new STR-based targets in the treatment of cancer. |
| first_indexed | 2024-03-07T15:03:55Z |
| format | Article |
| id | doaj.art-085a44ee693d48998da3663d5990326d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:03:55Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-085a44ee693d48998da3663d5990326d2024-03-05T18:57:39ZengNature PortfolioScientific Reports2045-23222024-02-0114111110.1038/s41598-024-53739-0Short tandem repeat mutations regulate gene expression in colorectal cancerMax A. Verbiest0Oxana Lundström1Feifei Xia2Michael Baudis3Tugce Bilgin Sonay4Maria Anisimova5Institute of Computational Life Sciences, Zurich University of Applied SciencesInstitute of Computational Life Sciences, Zurich University of Applied SciencesInstitute of Computational Life Sciences, Zurich University of Applied SciencesDepartment of Molecular Life Sciences, University of ZurichInstitute of Computational Life Sciences, Zurich University of Applied SciencesInstitute of Computational Life Sciences, Zurich University of Applied SciencesAbstract Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression data to study the gene regulatory effects of STR mutations in CRC. We confirm that STR mutability in CRC highly depends on the MSI status, repeat unit size, and repeat length. Furthermore, we present a set of 1244 putative expression STRs (eSTRs) for which the STR length is associated with gene expression levels in CRC tumours. The length of 73 eSTRs is associated with expression levels of cancer-related genes, nine of which are CRC-specific genes. We show that linear models describing eSTR-gene expression relationships allow for predictions of gene expression changes in response to eSTR mutations. Moreover, we found an increased mutability of eSTRs in MSI tumours. Our evidence of gene regulatory roles for eSTRs in CRC highlights a mostly overlooked way through which tumours may modulate their phenotypes. Future extensions of these findings could uncover new STR-based targets in the treatment of cancer.https://doi.org/10.1038/s41598-024-53739-0 |
| spellingShingle | Max A. Verbiest Oxana Lundström Feifei Xia Michael Baudis Tugce Bilgin Sonay Maria Anisimova Short tandem repeat mutations regulate gene expression in colorectal cancer Scientific Reports |
| title | Short tandem repeat mutations regulate gene expression in colorectal cancer |
| title_full | Short tandem repeat mutations regulate gene expression in colorectal cancer |
| title_fullStr | Short tandem repeat mutations regulate gene expression in colorectal cancer |
| title_full_unstemmed | Short tandem repeat mutations regulate gene expression in colorectal cancer |
| title_short | Short tandem repeat mutations regulate gene expression in colorectal cancer |
| title_sort | short tandem repeat mutations regulate gene expression in colorectal cancer |
| url | https://doi.org/10.1038/s41598-024-53739-0 |
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