Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer
Language English Country Great Britain, England Media print
Document type Journal Article, Observational Study, Research Support, Non-U.S. Gov't
PubMed
33319241
DOI
10.1093/carcin/bgaa136
PII: 6034128
Knihovny.cz E-resources
- MeSH
- 3' Untranslated Regions genetics MeSH
- Chemotherapy, Adjuvant MeSH
- Genetic Predisposition to Disease MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms blood genetics mortality therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local epidemiology prevention & control MeSH
- RNA, Messenger blood genetics MeSH
- MicroRNAs blood metabolism MeSH
- Follow-Up Studies MeSH
- Organic Anion Transporters genetics MeSH
- Prognosis MeSH
- Organic Cation Transport Proteins genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Organic Cation Transporter 2 genetics MeSH
- Binding Sites genetics MeSH
- Computational Biology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3' Untranslated Regions MeSH
- RNA, Messenger MeSH
- MicroRNAs MeSH
- Organic Anion Transporters MeSH
- Organic Cation Transport Proteins MeSH
- SLC22A2 protein, human MeSH Browser
- SLCO3A1 protein, human MeSH Browser
- solute carrier family 22 (organic cation transporter), member 3 MeSH Browser
- Organic Cation Transporter 2 MeSH
One of the principal mechanisms of chemotherapy resistance in highly frequent solid tumors, such as colorectal cancer (CRC), is the decreased activity of drug transport into tumor cells due to low expression of important membrane proteins, such as solute carrier (SLC) transporters. Sequence complementarity is a major determinant for target gene recognition by microRNAs (miRNAs). Single-nucleotide polymorphisms (SNPs) in target sequences transcribed into messenger RNA may therefore alter miRNA binding to these regions by either creating a new site or destroying an existing one. miRSNPs may explain the modulation of expression levels in association with increased/decreased susceptibility to common diseases as well as in chemoresistance and the consequent inter-individual variability in drug response. In the present study, we investigated whether miRSNPs in SLC transporter genes may modulate CRC susceptibility and patient's survival. Using an in silico approach for functional predictions, we analyzed 26 miRSNPs in 9 SLC genes in a cohort of 1368 CRC cases and 698 controls from the Czech Republic. After correcting for multiple tests, we found several miRSNPs significantly associated with patient's survival. SNPs in SLCO3A1, SLC22A2 and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk. To the best of our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to SLC transporter genes and their impact on CRC susceptibility or patient's prognosis.
Candiolo Cancer Institute FPO IRCCS Candiolo Italy
Department of Biology University of Pisa Via Derna Pisa Italy
Department of Oncology Thomayer Hospital Videnska Prague Czech Republic
Department of Surgery Thomayer University Hospital Videnska Prague Czech Republic
IIGM Italian Institute for Genomic Medicine Candiolo Italy
Institute for Clinical and Experimental Medicine IKEM Prague Czech Republic
Toxicogenomics Unit National Institute of Public Health Srobarova Prague Czech Republic
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