RGD Reference Report - The polymorphisms of miRNA-binding site in MLH3 and ERCC1 were linked to the risk of colorectal cancer in a case-control study. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The polymorphisms of miRNA-binding site in MLH3 and ERCC1 were linked to the risk of colorectal cancer in a case-control study.

Authors: Zhang, Qianye  Zheng, Xiao  Li, Xiaoxia  Sun, Deyu  Xue, Ping  Zhang, Guopei  Xiao, Mingyang  Cai, Yuan  Jin, Cuihong  Yang, Jinghua  Wu, Shengwen  Lu, Xiaobo 
Citation: Zhang Q, etal., Cancer Med. 2018 Apr;7(4):1264-1274. doi: 10.1002/cam4.1319. Epub 2018 Mar 8.
RGD ID: 153344543
Pubmed: PMID:29516665   (View Abstract at PubMed)
PMCID: PMC5911615   (View Article at PubMed Central)
DOI: DOI:10.1002/cam4.1319   (Journal Full-text)

Colorectal cancer (CRC), as a malignant tumor of lower digestive tract, has been found to have an increasing morbidity and mortality in China. It was particularly important to find some earlier biomarkers to predict the risk and prognosis. In this study, several polymorphisms on 3'UTR of three DNA repair genes including MLH3 rs10862, ERCC1 rs3212986, ERCC1 rs735482, ERCC1 rs2336219, and OGG1 rs1052133 were chosen by bioinformatics exploration, and then, a case-control study of 200 CRC cases and controls was performed. Furthermore, a dual-luciferase assay was also carried out to certify whether the candidate miRNA can regulate its target gene and the selected SNPs have a valid effect on the target miRNA. Finally, both of ERCC1 rs3212986 and MLH3 rs108621 were shown to be associated with the risk of CRC. Comparing with rs3212986 CC genotype, AA was at a higher risk (OR = 3.079, 95% CI: 1.192-7.952). For MLH3 rs108621, comparing with TT genotype, CC and TC were at a higher risk of CRC in male (OR = 5.171, 95% CI: 1.009-26.494; OR = 1.904, 95% CI: 1.049-3.455). Interestingly, an analysis combining both ERCC1 rs3212986 and MLH3 rs108621 also showed an increased risk of CRC. In addition, a dual-luciferase assay showed that miR-193a-3p could regulate MLH3, and the polymorphism rs108621 could alter the miR-193a-3p binding to MLH3. Therefore, MLH3 rs108621 may be associated with the risk of CRC due to the effect of miR-193a-3p on MLH3, which reminded the possibility as potential susceptibility biomarkers to predict the risk of CRC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer sexual_dimorphism IAGP 153344543DNA:SNP:3'utr: (rs3212986) (human)RGD 
colorectal cancer sexual_dimorphism ISOERCC1 (Homo sapiens)153344543; 153344543DNA:SNP:3'utr: (rs3212986) (human)RGD 
colorectal cancer sexual_dimorphism IAGP 153344543DNA:SNP:3'utr: (rs108621)RGD 
colorectal cancer sexual_dimorphism ISOMLH3 (Homo sapiens)153344543; 153344543DNA:SNP:3'utr: (rs108621)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm of the large intestine sexual_dimorphism IAGP 153344543DNA:SNP:3'utr: (rs3212986) (human)RGD 
Neoplasm of the large intestine sexual_dimorphism IAGP 153344543DNA:SNP:3'utr: (rs108621)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ercc1  (ERCC excision repair 1, endonuclease non-catalytic subunit)
Mlh3  (mutL homolog 3)

Genes (Mus musculus)
Ercc1  (excision repair cross-complementing rodent repair deficiency, complementation group 1)
Mlh3  (mutL homolog 3)

Genes (Homo sapiens)
ERCC1  (ERCC excision repair 1, endonuclease non-catalytic subunit)
MLH3  (mutL homolog 3)


Additional Information