Dataset Information

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

ABSTRACT: Background: Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients.

Methods: In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated.

Results: The rs2910164C allele (OR?=?1.56, 95% CI?=?1.10-2.21, p = 0.012) and CC genotype (OR?=?2.93, 95% CI?=?1.07-7.9, p = 0.034, respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR?=?0.57, 95%?CI?=?0.33-0.99, p = 0.048) and the A allele frequency (OR?=?0.58, 95%?CI?=?0.35-0.98, p = 0.043) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR?=?0.44, 95%?CI?=?0.21-0.90, p = 0.024). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC.

Conclusion: Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

SUBMITTER: Dezfuli NK

PROVIDER: S-EPMC7700047 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

Dezfuli Neda K NK Adcock Ian M IM Alipoor Shamila D SD Seyfi Sharareh S Salimi Babak B Mafi Golchin Maryam M Dalil Roofchayee Neda N Varhram Mohammad M Mortaz Esmaeil E

Canadian respiratory journal 20201120

<h4>Background</h4>Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed as ...[more]

PMID: 33294082

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Project description:BackgroundNon-small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients.MethodsThirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry.ResultsmiR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=-0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype.ConclusionsThe current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages.

Project description:BackgroundRheumatoid arthritis (RA) is a chronic inflammatory condition that impacts not only the musculoskeletal system but also various other systems in the body, including the cutaneous, ocular, respiratory, cardiovascular, and circulatory systems. MicroRNAs (miRNAs) are a class of naturally occurring and highly conserved transcripts that primarily function in the regulation of gene expression. They accomplish this by facilitating the degradation of messenger RNA (mRNA) or by repressing mRNA translation. miRNAs are well-known regulators of a variety of cellular processes. Therefore, we aimed to detect the impact of miR-155 rs767649 polymorphism on RA activity.MethodsThis case-control study included 66 Egyptian patients with RA who visited Al-Zhraa University Hospital, Internal Medicine Department, Cairo, Egypt, and 50 apparently healthy control subjects matched for age and sex. The participants were subjected to full clinical evaluation, including assessments of the disease activity score (DAS), erythrocyte sedimentation rate (ESR), liver and kidney function, anti-cyclic citrullinated peptide antibody (anti-CCP), and miR-155 polymorphism using real-time polymerase chain reaction (PCR).ResultsIn the RA group, the majority (98.5%) were female, with a mean age of 43 years, while in the control group, 94% were female, with a mean age of 43.4 years. Comparison of laboratory parameters indicated significantly lower hemoglobin levels, higher ESR, and higher serum creatinine and anti-CCP levels in the RA group than in the control group. The RA group had a significantly higher frequency of TT genotypes and significantly lower frequencies of TA and TT genotypes than the control group. Considering the TT genotype and T allele as references, TA, AA, and TA/AA genotypes in the dominant model; AA in the recessive model; and A allele were significantly associated with protective effects against RA development (p<0.05, odds ratio<1).Conclusionrs767649, the functional variant of miR-155, plays an important role in susceptibility to the increased risk of RA, suggesting that miR-155 can be used as a therapeutic target for the treatment of Egyptian patients with RA.

Project description:To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer.The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons.The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.

Dataset Information

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

Publications

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

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