Dataset Information

Genetic associations between the miRNA polymorphisms miR-130b (rs373001), miR-200b (rs7549819), and miR-495 (rs2281611) and colorectal cancer susceptibility.

ABSTRACT:

Background

Recent studies have extensively investigated the role of miRNAs in colorectal cancer (CRC), and several associations have been reported. In addition, single nucleotide polymorphisms (SNPs) in promoter regions of miRNAs have been shown to affect miRNA expression. Therefore, we aimed to analyze the effect of miRNA polymorphisms on CRC susceptibility.

Methods

We conducted association studies on the relationships between the miRNA polymorphisms miR-130bT > C rs373001, miR-200bT > C rs7549819, and miR-495A > C rs2281611 and CRC with 472 CRC patients and 399 control subjects in Korea.

Results

Multivariate logistic regressions of the CRC subgroups showed that the miR-495CC genotype associated with rectal cancer (AA+AC vs. CC; adjusted odds ratio (AOR) for CC, 1.592; 95% confidence interval (CI), 1.071-2.368; P = 0.022). The gene-environment combinatorial analysis showed that the combination of miR-495A > C and low plasma folate contributed to an increased risk of rectal cancer (AA+AC vs. CC; AOR for CC, 3.829; 95% CI, 1.577-9.300; P = 0.003). In the survival analysis, miR-200bT > C associated with CRC patient mortality (TT vs TC + CC; adjusted hazard ratio for TC + CC, 0.592; 95% CI, 0.373-0.940; P = 0.026).

Conclusion

In this study, we found that miR-200b and miR-495 polymorphisms are involved in CRC susceptibility and prognosis.

SUBMITTER: Kim EG

PROVIDER: S-EPMC6532172 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Genetic associations between the miRNA polymorphisms miR-130b (rs373001), miR-200b (rs7549819), and miR-495 (rs2281611) and colorectal cancer susceptibility.

Kim Eun-Gyo EG Kim Jung Oh JO Park Han Sung HS Ryu Chang Soo CS Oh Jisu J Jun Hak Hoon HH Kim Jong Woo JW Kim Nam Keun NK

BMC cancer 20190522 1

<h4>Background</h4>Recent studies have extensively investigated the role of miRNAs in colorectal cancer (CRC), and several associations have been reported. In addition, single nucleotide polymorphisms (SNPs) in promoter regions of miRNAs have been shown to affect miRNA expression. Therefore, we aimed to analyze the effect of miRNA polymorphisms on CRC susceptibility.<h4>Methods</h4>We conducted association studies on the relationships between the miRNA polymorphisms miR-130bT > C rs373001, miR-2 ...[more]

PMID: 31117970

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Project description:Although microRNA (miRNA)-mediated functions and gene expression regulation are involved in the susceptibility to vascular diseases, the potential effect of miRNA polymorphisms on the susceptibility of patients to hypertension (HTN) remains to be sufficiently elucidated. Therefore, the present study aimed to identify the potential association between miRNA (miR)-200bT>C (rs7549819) and miR-495A>C (rs2281611) polymorphisms, which may be implicated in stroke and vascular pathogenesis, and the susceptibility to HTN and relevant risk factors in a Korean cohort recruited from Jeju National University Hospital (Jeju, South Korea). Using an analysis of PCR-restriction fragment length polymorphism, genotype analysis was conducted to assess the frequency of miR-200bT>C and miR-495A>C gene polymorphisms in the HTN group (n=232) and the non-HTN healthy control group (n=247). The results showed significant differences in the genotype distributions of the miR-495A>C polymorphism between the HTN and control groups, specifically with the CC genotype and C allele. However, neither the miR-200bT>C nor the dominant and recessive models were found to be distributed differently between the two groups. Following analysis of the genotype combination of the single nucleotide polymorphisms, the TC/CC and CC/CC combined genotypes of the miR-200bT>C and miR-495A>C polymorphisms were observed to be associated with susceptibility to HTN. The haplotype results demonstrated that the allele combination frequency of haplotype C-A was significantly different between the two groups. The stratified analysis revealed that the miR-200b and miR-495 polymorphisms are associated with the risk of HTN, exhibiting differences in the levels of body-mass index (<28.12 kg/m2), fasting blood glucose (<106.26 mg/dl), high-density lipoprotein cholesterol (<44.29 mg/dl) and systolic blood pressure (≥132.67 mmHg). Data from the present study suggested that the variant of miR-495A>C polymorphism and allelic combinations (haplotype C-A of miR-200bT>C/miR-495A>C) can increase hypertension susceptibility among a Korean population.

Project description:Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-d-old male Jianzhou big-ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes, respectively, and differentiation was induced by 50μM oleic acid for 48 h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPβ, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1, and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis, and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB, and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3'UTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 were conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining, and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPβ, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL, and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPβ, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL, and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect.

Dataset Information

Genetic associations between the miRNA polymorphisms miR-130b (rs373001), miR-200b (rs7549819), and miR-495 (rs2281611) and colorectal cancer susceptibility.

Background

Methods

Results

Conclusion

Publications

Genetic associations between the miRNA polymorphisms miR-130b (rs373001), miR-200b (rs7549819), and miR-495 (rs2281611) and colorectal cancer susceptibility.

Similar Datasets

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