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Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5rs34324334* and RANrs14035*) with Susceptibility to Hepatocellular Carcinoma.

ABSTRACT: Numerous reports have explored the roles of different genetic variants in miRNA biogenesis mechanisms and the progression of various types of carcinomas. The goal of this study is to explore the association between XPO5*rs34324334 and RAN*rs14035 gene variants and susceptibility to hepatocellular carcinoma (HCC). In a cohort of 234 participants (107 HCC patients and 127 unrelated cancer-free controls) from the same geographic region, we characterized allelic discrimination using PCR-RFLP and performed subgroup analysis and multivariate regression. We found that the frequency of the XPO5*rs34324334 (A) variant was correlated with elevated risk of HCC under allelic (OR = 10.09, p-value < 0.001), recessive (OR = 24.1, p-value < 0.001), and dominant (OR = 10.1, p-value < 0.001) models. A/A genotype was associated with hepatitis C cirrhosis (p-value = 0.012), ascites (p-value = 0.003), and higher levels of alpha-fetoproteins (p-value = 0.011). Carriers of the RAN*rs14035 (T) variant were more likely to develop HCC under allelic (OR = 1.76, p-value = 0.003) and recessive (OR = 3.27, p-value < 0.001) models. Our results suggest that XPO5*rs34324334 and RAN*rs14035 variants are independent risk factors for developing HCC.

SUBMITTER: Elsalahaty MI

PROVIDER: S-EPMC10302587 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5rs34324334 and RANrs14035) with Susceptibility to Hepatocellular Carcinoma.

Elsalahaty Mohamed I MI Salama Afrah F AF Diab Thoria T Ghazy Medhat M Toraih Eman E Elshazli Rami M RM

Journal of personalized medicine 20230606 6

Numerous reports have explored the roles of different genetic variants in miRNA biogenesis mechanisms and the progression of various types of carcinomas. The goal of this study is to explore the association between XPO5*rs34324334 and RAN*rs14035 gene variants and susceptibility to hepatocellular carcinoma (HCC). In a cohort of 234 participants (107 HCC patients and 127 unrelated cancer-free controls) from the same geographic region, we characterized allelic discrimination using PC ...[more]

PMID: 37373948

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Project description:BackgroundMicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end-stage renal disease (ESRD).MethodA total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real-Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out.ResultsCarrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15-0.62, dominant model: OR = 0.35, 95% CI = 0.17-0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11-0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22-0.92, and allelic model: OR = 0.46, 95% CI = 0.34-0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28-11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10-409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A-A-T-T: OR = 9.49, 95%CI = 2.48-36.31 (P = .001) and G-A-T-T: OR = 5.92, 95%CI = 1.77-19.83 (P = .004), respectively].ConclusionVariants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.

Project description:BackgroundHepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV).MethodsDatabases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines.ResultsA total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs.ConclusionMiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.

Dataset Information

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5rs34324334* and RANrs14035*) with Susceptibility to Hepatocellular Carcinoma.

Publications

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (<i>XPO5rs34324334</i> and <i>RANrs14035</i>) with Susceptibility to Hepatocellular Carcinoma.

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Dataset Information

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma.

Publications

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (<i>XPO5*rs34324334</i> and <i>RAN*rs14035</i>) with Susceptibility to Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5rs34324334* and RANrs14035*) with Susceptibility to Hepatocellular Carcinoma.

Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (<i>XPO5rs34324334</i> and <i>RANrs14035</i>) with Susceptibility to Hepatocellular Carcinoma.