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

Autor: Sivakumar Selvaraj, Zioni Sangeetha Shankaran, Mohanapriya Chinambedu Dandapani, Arvind Ramanathan, Thanka Johnson, Sai Sushmitha Kontham, Charles Emmanuel Jebaraj Walter
Rok vydání: 2020
Předmět:
Zdroj: Meta Gene. 24:100654
ISSN: 2214-5400
Popis: Gastrointestinal (GI) cancers are among the prime causes for cancer deaths worldwide demanding competent methods for prediction and diagnosis. MiR-146a, a key modulator of immunity and inflammation, harbors a single nucleotide polymorphism (SNP) rs2910164 which leads to ineffectual suppression of the miR146a targets TNF receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1). In the current study, we aimed to bring out the relationship of rs2910164 with GI cancers and their impact on the target genes. We conducted a case-control study with 180 gastrointestinal cancer patient and 230 cancer-free control recruits. The polymorphism was genotyped using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method and the target gene expression was done by quantitative Real Time PCR. Our study reported that the polymorphism studied had no association with GI cancers as such, but it was significantly associated with the risk of human colorectal cancer (CRC). Following these results, expression of Nuclear factor kappa B (NF-κB), TRAF6 and IRAK1 were analyzed in the archived CRC tissues for the three genotype carriers. The expression of IRAK1 and TRAF6 genes were found to be elevated in the GC and CC carriers and NF-κB which regulates the expression of miR-146a by negative feedback mechanism was also elevated in the mutant genotypes. This is the first study to show that miR-146a polymorphism increased the susceptibility to CRC apparently by influencing the expression of its target genes in an Indian population.
Databáze: OpenAIRE
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