Metformin and long non-coding RNAs in breast cancer.

Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical and pathological features. Recent studies also investigated the roles of metformin treatment as the firstline treatment for type 2 diabetes (T2D) played in lncRNAs expression/regulation or BC incidence, outcome, mortality and survival, separately. This comprehensive study aimed to review lncRNAs associated with BC features and identify metformin-regulated lncRNAs and their mechanisms of action on BC or other types of cancers. Finally, metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, by several molecular mechanisms have been described in this review. In addition, metformin action on other types of cancers by regulating ten lncRNAs including AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, H19, MALAT1, AFAP1-AS1, AC026904.1 is described.

Haplotypic variants of COVID-19 related genes are associated with blood pressure and metabolites levels.

The genetic association of coronavirus disease 2019 (COVID-19) with its complications has not been fully understood. This study aimed to identify variants and haplotypes of candidate genes implicated in COVID-19 related traits by combining the literature review and pathway analysis. To explore such genes, the protein-protein interactions and relevant pathways of COVID-19-associated genes were assessed. A number of variants on candidate genes were identified from Genome-wide association studies (GWASs) which were associated with COVID-19 related traits (p ˂ 10-6 ). Haplotypic blocks were assessed using haplotypic structures among the 1000 Genomes Project (r2 ≥ 0.8, D' ≥ 0.8). Further functional analyses were performed on the selected variants. The results demonstrated that a group of variants in ACE and AGT genes were significantly correlated with COVID-19 related traits. Three haplotypes were identified to be involved in the blood metabolites levels and the development of blood pressure. Functional analyses revealed that most GWAS index variants were expression quantitative trait loci and had transcription factor binding sites, exonic splicing enhancers or silencer activities. Furthermore, the proxy haplotype variants, rs4316, rs4353, rs4359, and three variants, namely rs2493133, rs2478543, and rs5051, were associated with blood metabolite and systolic blood pressure, respectively. These variants exerted more regulatory effects compared with other GWAS variants. The present study indicates that the genetic variants and candidate haplotypes of COVID-19 related genes are associated with blood pressure and blood metabolites. However, further observational studies are warranted to confirm these results.

Role of genetic polymorphisms in recurrent aphthous stomatitis: A systematic review and meta-analysis.

Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with unknown etiology. Identifying the genetic markers can improve medical care and prevention of RAS. Genetics variants inflammatory agents are associated with the risk of RAS. Thus, this meta-analysis aimed to investigate the genetic polymorphisms in RAS. Electronic literature search was carried out on Scopus, PubMed, and Web of Science (WOS). The references of relevant reviews were also manually checked. The observational studies till the end of 2020 were included. Odds ratio (OR) was estimated by fixed and random effect model. Seventeen polymorphisms in 23 studies were included in analysis. Pooled analysis performed for 12 polymorphisms (IL-2+166, IL-2-330, IL-4-590, IL-4 RA1902, IL-6-597, TNF-α-308, NLRP3(rs4612666, rs10754558), MMP2- rs2285053, MMP9- rs11697325, MMP9- rs3918242, MMP9- rs17576, IL-1a-889, IL-10-819, and IL-12+1188). The meta-analyses carried out for six polymorphisms (IL-1ß-511, IL-1ß+3954, IL-6-174, IL-10-592, IL-10-1082, and serotonin transporter). There were following significant results for IL-10, 819 in allelic:1.46(1.04-2.05) and homozygote: 1.61(1.08-2.39) models, serotonin Transporter in allelic:0.53(0.40-0.71), recessive:0.56(0.35-0.90), dominant:0.35(0.22-0.57) and homozygote:0.30(0.17-0.54) models. IL-1ß-511 in dominant 0.69(0.50-0.95) and overdominant 0.73(0.55-0.96) models, IL-1ß+3954 in allelic 1.25(1.05-1.50), homozygote 1.67(1.05-2.63) and dominant 1.26(1.01-1.57) models, IL-6-174 in dominant 2.24(1.36-3.67), IL-10-592 in homozygote 0.41(0.23-0.72) and dominant 0.55(0.33-0.93), IL-10-1082 in allelic 1.19(1.01-1.39) and dominant 1.29(1.02-1.64). In conclusion, serotonin transporter(L/S), IL-10-819(T/C), IL-10-592(C/A), IL-10-1082(G/A), IL-1ß-511(C/T), IL-6-174(G/C), and IL-1ß+3954 (T/C) polymorphisms are associated with susceptibility to RAS. These variants could be potential predictors of RAS and could be used for the developing clinically effective genetic panel for RAS.

Association of miRNA targetome variants in LAMC1 and GNB3 genes with colorectal cancer and obesity.

BACKGROUND: Colorectal cancer (CRC) is one of the most common obesity-associated cancers. Inflammation is also considered the most important factor between obesity and CRC. This study aimed to examine miRNAs binding sites variants on inflammatory genes identified using bioinformatics and systematic approach on clinical samples that were collected from CRC patients and controls. METHODS: The candidate variants related to CRC inflammatory genes were obtained from genome-wide association studies and their population-specific haplotypes. The variants were analyzed according to their genomic position on the miRNA targetome. Targetome variants in inflammation-related genes were selected for genetic association study by TaqMan genotyping assay. RESULTS: The GG genotype of rs7473 decreased the risk of obesity (p < 0.05). Heterozygous genotype (GA) of rs1547715 decreased the risk of CRC (p < 0.05). In the rs7473/rs1547715 genotype and haplotype, the frequencies of AA/GA and GG/AA lessened in CRC and obesity, respectively (p < 0.05). CONCLUSIONS: The variants of rs7473 and rs1547715 were associated with obesity and CRC, respectively. The above-mentioned associations could be made based on the interactions of these variants with miRNAs.

The role of inflammatory miRNA-mRNA interactions in PBMCs of colorectal cancer and obesity patients.

INTRODUCTION: Inflammation is a critical hallmark in obesity and colorectal cancer (CRC). This study aimed to investigate effective microRNA (miRNA)-messenger RNA (mRNA) interactions on inflammatory networks involved in obesity and CRC. METHODS: The literature searches were applied to identify genes expression reported on peripheral blood mononuclear cells (PBMCs) and/or blood of CRC subjects and to find inflammatory miRNA  in blood samples. Furthermore, bioinformatics analysis was utilized to find inflammatory miRNA:mRNA interactions of the genes. Finally, a case-control study was set to investigate the expression of LAMC1 and GNB3 genes besides miR-10b, miR-506-3p, miR-150-5p, and miR-124-3p in CRC and control subjects. RESULTS: The expression of LAMC1 gene in healthy control groups was associated with body mass index (BMI) (p < .05). The level of miR-10b (p < .001), miR-506 (p < .001), and miR-124 (p <. 001) were significantly increased in PBMCs of CRC patients, while they were not associated with BMI. The level of miR-150 was associated with BMI in healthy subjects (p < .05). CONCLUSIONS: The changes in the level of miR-506 and miR-124 in CRC patients may be associated with the regulatory role of these miRNAs on LAMC1 expression. The LAMC1 may be related to BMI, however, more observational studies on other populations are needed.