Single-nucleotide polymorphism rs17548629 in RIPK1 gene may be associated with lung cancer in a young and middle-aged Han Chinese population

Abstract

Background Genetic biomarkers of lung cancer (LC) susceptibility may provide a basis for treatment and prevention. This study analyzed an association between SNPs (single nucleotide polymorphisms) in the complementary region of the 3′-UTR (3' untranslated region) of microRNAs of the gene RIPK1 (receptor-interacting serine/threonine-protein kinase 1) and LC among an adult Han Chinese population aged younger than 60 years. Also explored the effect of regulation of the RIPK1 gene via rs17548629 and microRNA-1197 on the occurrence of LC. Methods RIPK1 variants (rs17548629, rs77736895) were determined in a population of 571 adults (younger than 60 years) with LC, and 609 gender- and age-matched healthy individuals. Bioinformatics methods predicted the microRNAs bound to rs17548629. Dual luciferase reporter assay was performed to confirm the presence of both rs17548629 and the predicted microRNA. Results A mutation (T) of rs17548629 was associated with an increased risk for LC in this population under the codominant and recessive genetic models. The risk of lung adenocarcinoma in rs17548629 mutant carriers was 1.769-fold higher than that of the wildtype. In vitro , the luciferase activity of co-transfected mutant psiCHECK2- RIPK1 and microRNA-1197 mimics was less than that of the group transfected with microRNA-1197 mimics only. Factorial analysis indicated interactions between microRNA-1197 mimics and genotypes of rs17548629. Conclusion A mutation (T) of rs17548629 may increase the risk of LC/lung adenocarcinomain adult Han populations younger than 60 years. When carrying the T allele, rs17548629 may be the target of hsa-miR-1197. This mutation may affect transcriptional level of the RIPK1, thereby promoting the occurrence of LC.

Von Hippel-Lindau gene single nucleotide polymorphism (rs1642742) may be related to the occurrence and metastasis of HBV-related hepatocellular carcinoma

“…Our results suggested that there was correlation between rs1642742 and metastasis and the allele A might be associated with tumor metastasis. Of course, the correlation between SNP and tumor metastasis had been reported in previous literatures, including lung cancer, breast cancer, gastric cancer, prostate cancer, and so on [42–45] . Rs1642742 is residing in the 3′UTR of the VHL , which plays an important role in mRNA translocation, stability and translational regulation.…”

“…Of course, the correlation between SNP and tumor metastasis had been reported in previous literatures, including lung cancer, breast cancer, gastric cancer, prostate cancer, and so on. [42][43][44][45] Rs1642742 is residing in the 3 0 UTR of the VHL, which plays an important role in mRNA translocation, stability and translational regulation. The variant allele of rs1642742 may affect the ability of miRNA to bind to its sequence, which in turn affects the VHL gene expression and may lead to tumor metastasis.…”

A novel defined necroptosis-related lncRNAs signature for predicting the prognosis of non-small cell lung cancer

“…Necroptosis is a new programmed form of necrotic cells different from apoptosis, and anti-tumor immunity enhancement mediated by CD8 + leukocytes upon RIPK1 and RIPK3 activation in the tumor microenvironment (TME) comprises its main mechanism. Meanwhile, necroptosis can accelerate the apoptosis and necrosis of malignant tumor cells by producing immunosuppressive TME through CXCL1 and Mincle, which suggests necroptosis to be a potential immunotherapeutic target against malignant tumors (11)(12)(13)(14).…”