microRNA-146a gene polymorphism alters human colorectal cancer susceptibility and influences the expression of its target genes in toll-like receptor (TLR) pathway

Shankaran, Zioni Sangeetha; Walter, Charles Emmanuel Jebaraj; Ramanathan, Arvind; Dandapani, Mohanapriya Chinambedu; Selvaraj, Sivakumar; Kontham, Sai Sushmitha; Thanka, J

doi:10.1016/j.mgene.2020.100654

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Fish innate immunity is the first line of host defense and mainly comprises pattern recognition receptor signaling pathways ( 13 , 53 ). The recently identified miRNAs play important roles in the regulation of the inflammatory and immune responses, indicating a miRNA-mediated TLR/NF-κB signaling pathway ( 54 , 55 ). In teleost fish, it is worth noting that the miRNAs were significantly related to immune defense, such as the NLR, apoptosis, JAK-STAT, and MAPK singling pathways that are involved in various biological processes ( 8 , 56 ), consistent with the results of this study on C. auratus .…”

Section: Discussionmentioning

confidence: 99%

Multiomics analysis revealed miRNAs as potential regulators of the immune response in Carassius auratus gills to Aeromonas hydrophila infection

Huo

Bai

et al. 2023

Front. Immunol.

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The gill of fish is an important immune organ for pathogen defense, but its microRNA (miRNA) expression and regulatory mechanism remain unclear. In this study, we report on the histopathological and immunohistochemical features of the gills of the crucian carp Carassius auratus challenged with Aeromonas hydrophila. Small RNA libraries of the gills were constructed and sequenced on the Illumina HiSeq 2000 platform. A total of 1,165 differentially expressed miRNAs (DEMs) were identified in gills, of which 539 known and 7 unknown DEMs were significantly screened (p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the potential target genes/proteins were primarily involved in 33 immune-related pathways, in which the inflammatory responses were focused on the Toll-like receptor (TLR), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) signaling pathways. Moreover, the expression levels of 14 key miRNAs (e.g., miR-10, miR-17, miR-26a, miR-144, miR-145, and miR-146a) and their target genes (e.g., TNFα, TLR4, NF-κB, TAB1, PI3K, and IRAK1) were verified. In addition, the protein levels based on isobaric tags for relative and absolute quantification (iTRAQ) were significantly associated with the results of the quantitative real-time PCR (qRT-PCR) analysis (p < 0.01). miR-17/pre-miR-17 were identified in the regulation expression of the NF-κB target gene, and the phylogenetic tree analysis showed that the pre-miR-17 of C. auratus with the closest similarity to the zebrafish Danio rerio is highly conserved in teleosts. This is the first report of the multi-omics analysis of the miRNAs and proteins in the gills of C. auratus infected with A. hydrophila, thus enriching knowledge on the regulation mechanism of the local immune response in Cyprinidae fish.

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Section: Discussionmentioning

confidence: 99%

Multiomics analysis revealed miRNAs as potential regulators of the immune response in Carassius auratus gills to Aeromonas hydrophila infection

Huo

Bai

et al. 2023

Front. Immunol.

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“…However, no significant difference was found between allele and genotype at position rs57095329. In 2020 in the Indian population determined that the GC genotype had a significant influence on the susceptibility to colorectal cancers [ 64 ]. A previous study [ 65 ], found significant differences in the allele G and CC genotype of miR-146 C > G SNP between the pulmonary TB patients and healthy controls in the Kazak population, while in the Uygur population there were no significant differences in the frequencies of alleles and genotypes of miR-146a.…”

Section: Discussionmentioning

confidence: 99%

Association between risk of brucellosis and genetic variations in MicroRNA-146a

et al. 2021

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Background Single nucleotide polymorphisms (SNPs) are the most common types of DNA changes in the human genome that leading to phenotypic differences in humans. MicroRNAs (miRNAs) are usually affected by various bacterial infections, and they are involved in controlling the immune responses. MicroRNA-146a (miR-146a) plays an essential role in the development of infectious and inflammatory diseases. The aim of the present study was to investigate the association between risk of brucellosis and genetic variations in miR-146a. Methods This case–control study was conducted on 108 Brucellosis patients and 108 healthy controls. We genotyped two SNPs (rs2910164 and rs57095329) of the miR-146a using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. Results The rs2910164 SNP was significantly associated with brucellosis in co-dominant [OR = 4.27, 95% CI = (2.35–7.79, P = 0.001] and dominant [OR = 3.52, 95% CI = (1.97–6.30, P = 0.001] models. Co-dominant (P = 0.047) and recessive (P = 0.018) models were significant at position rs57095329 between the two groups of patient and healthy. The A C haplotype (rs2910164 and rs57095329) was associated with brucellosis in the assessed population [OR (95% CI) = 1.98 (1.22–3.20), P = 0.0059]. Conclusions Consequently, our study demonstrated significant differences in genotype and haplotype frequencies of miR-146a variants between brucellosis patients and controls. Further studies on the larger sample sizes are required to verify the observed associations.

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“…For example, The Taganov et al (18) study found that the expression of adult miRNA-146a in THP-1 cells is increased with lipopolysaccharide (LPS) microbial components and cytokines, including IL-1β and TNF-α. Shankaran et al (7) showed that miR-146a polymorphism increased the sus-ceptibility to CRC apparently by influencing the expression of its target genes in an Indian population.…”

Section: Discussionmentioning

confidence: 99%

“…This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. pathway of two receptors, toll-like and cytokine including TNF-α in response of the immune system to molecular patterns associated with various pathogens, thereby increasing the risk of cancer (7).…”

Section: Introductionmentioning

confidence: 99%

Molecular Analysis of rs2910164 Polymorphism and its Association with TNF-α Gene Expression in Colorectal Cancer

Hamta

Tolooi

2021

Jentashapir J Cell Mol Biol

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Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world, which has been diagnosed as the third most common cancer and the third leading cause of death. This cancer before the age of 50 is uncommon, and its prognosis is controversial, with many studies reporting a worse prognosis than in older patients and others showing no difference. In addition to factors, including diet, environmental factors, somatic and hereditary mutations, genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor-α (TNF-α) gene, may be involved in this cancer. Objectives: This study aimed to investigate the rs2910164 polymorphism from the miRNA146a gene and its association with the expression of TNF-α gene in CRC before and after the age of 50 for early diagnosis and treatment. Methods: In this study, 65 samples of cancerous lesions (37 cases over 50 years were considered the case group and 28 cases under 50 years were considered the control group) was collected from in an Iranian population. DNA was extracted from the samples, and rs2910164 polymorphism of the miRNA146a gene was investigated by PCR. Moreover, RNA was extracted from the samples, and the expression of the miRNA146a and TNF-α genes were evaluated. Finally, for data analysis, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used. Results: The frequency of GG, GC, and CC genotypes from rs2910164 polymorphism of miRNA146a gene in the control group was 0.29, 0.46, and 0.25, respectively, but in the case group it was 0.54, 0.38, and 0.08, respectively. The results also showed that the expression of miRNA146a (P = 0.00006) and TNF-α (P = 0.009) genes was higher in the case group than the control group. Conclusions: Based on the results of this study, a significant correlation was found between GG genotype and rs2910164 polymorphism of miRNA146a gene and TNF-α gene expression in the CRC samples. Therefore, investigation of these factors may be helpful in patients over 50 years with CRC.

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microRNA-146a gene polymorphism alters human colorectal cancer susceptibility and influences the expression of its target genes in toll-like receptor (TLR) pathway

Cited by 6 publications

References 31 publications

Multiomics analysis revealed miRNAs as potential regulators of the immune response in Carassius auratus gills to Aeromonas hydrophila infection

Multiomics analysis revealed miRNAs as potential regulators of the immune response in Carassius auratus gills to Aeromonas hydrophila infection

Association between risk of brucellosis and genetic variations in MicroRNA-146a

Molecular Analysis of rs2910164 Polymorphism and its Association with TNF-α Gene Expression in Colorectal Cancer

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