Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer

P. Bendova, B. Pardini, S. Susova, J. Rosendorf, M. Levy, P. Skrobanek, T. Buchler, J. Kral, V. Liska, L. Vodickova, S. Landi, P. Soucek, A. Naccarati, P. Vodicka, V. Vymetalkova

. 2021 ; 42 (3) : 378-394. [pub] 20210417

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, pozorovací studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21018817

Grantová podpora
NV17-30920A MZ0 CEP - Centrální evidence projektů

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21018817
003      
CZ-PrNML
005      
20210830100401.0
007      
ta
008      
210728s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/carcin/bgaa136 $2 doi
035    __
$a (PubMed)33319241
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Bendova, Petra $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Videnska, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
245    10
$a Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer / $c P. Bendova, B. Pardini, S. Susova, J. Rosendorf, M. Levy, P. Skrobanek, T. Buchler, J. Kral, V. Liska, L. Vodickova, S. Landi, P. Soucek, A. Naccarati, P. Vodicka, V. Vymetalkova
520    9_
$a 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.
650    _2
$a 3' nepřekládaná oblast $x genetika $7 D020413
650    _2
$a senioři $7 D000368
650    _2
$a vazebná místa $x genetika $7 D001665
650    _2
$a studie případů a kontrol $7 D016022
650    _2
$a adjuvantní chemoterapie $7 D017024
650    _2
$a kolorektální nádory $x krev $x genetika $x mortalita $x terapie $7 D015179
650    _2
$a výpočetní biologie $7 D019295
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a následné studie $7 D005500
650    _2
$a regulace genové exprese u nádorů $7 D015972
650    _2
$a genetická predispozice k nemoci $7 D020022
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a mikro RNA $x krev $x metabolismus $7 D035683
650    _2
$a lidé středního věku $7 D008875
650    _2
$a lokální recidiva nádoru $x epidemiologie $x prevence a kontrola $7 D009364
650    _2
$a přenašeče organických aniontů $x genetika $7 D027361
650    _2
$a proteiny přenášející organické kationty $x genetika $7 D027701
650    _2
$a transportér organických kationtů 2 $x genetika $7 D000075102
650    _2
$a jednonukleotidový polymorfismus $7 D020641
650    _2
$a prognóza $7 D011379
650    _2
$a messenger RNA $x krev $x genetika $7 D012333
655    _2
$a časopisecké články $7 D016428
655    _2
$a pozorovací studie $7 D064888
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Pardini, Barbara $u IIGM Italian Institute for Genomic Medicine, Candiolo, Italy $u Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
700    1_
$a Susova, Simona $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic $u Toxicogenomics Unit, National Institute of Public Health, Srobarova, Prague, Czech Republic
700    1_
$a Rosendorf, Jachym $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
700    1_
$a Levy, Miloslav $u Department of Surgery, Thomayer University Hospital, Videnska, Prague, Czech Republic
700    1_
$a Skrobanek, Pavel $u Department of Oncology, Thomayer Hospital, Videnska, Prague, Czech Republic
700    1_
$a Buchler, Tomas $u Department of Oncology, Thomayer Hospital, Videnska, Prague, Czech Republic
700    1_
$a Kral, Jan $u Institute for Clinical and Experimental Medicine, IKEM, Prague, Czech Republic
700    1_
$a Liska, Vaclav $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
700    1_
$a Vodickova, Ludmila $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Videnska, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
700    1_
$a Landi, Stefano $u Department of Biology, University of Pisa, Via Derna, Pisa, Italy
700    1_
$a Soucek, Pavel $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic $u Toxicogenomics Unit, National Institute of Public Health, Srobarova, Prague, Czech Republic
700    1_
$a Naccarati, Alessio $u IIGM Italian Institute for Genomic Medicine, Candiolo, Italy $u Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
700    1_
$a Vodicka, Pavel $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Videnska, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
700    1_
$a Vymetalkova, Veronika $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Videnska, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic $u Biomedical Centre and Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Alej Svobody, Pilsen, Czech Republic
773    0_
$w MED00001050 $t Carcinogenesis $x 1460-2180 $g Roč. 42, č. 3 (2021), s. 378-394
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33319241 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830100401 $b ABA008
999    __
$a ok $b bmc $g 1689796 $s 1139263
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 42 $c 3 $d 378-394 $e 20210417 $i 1460-2180 $m Carcinogenesis $n Carcinogenesis $x MED00001050
GRA    __
$a NV17-30920A $p MZ0
LZP    __
$a Pubmed-20210728

Najít záznam

Citační ukazatele

Možnosti archivace