Alternative splicing related genetic variants contribute to bladder cancer risk

Abstract

Emerging evidence has shown that aberrant alternative splicing (AS) events are involved in the carcinogenesis. The association between genetic variants in AS and bladder cancer susceptibility remains to be fully elucidated. We searched for single nucleotide polymorphisms (SNPs) which are located in splicing quantitative trait loci (sQTLs) in bladder cancer through CancerSplicingQTL database and the 1000 Genomes Project. A case‐control study including 580 cases and 1,101 controls was conducted to assess the association between the functional genetic variants and bladder cancer risk. Next, we used GTEx, TCGA, and GEO databases conducting sQTL analysis and gene expression differences analysis to evaluate the potential biological function of the candidate SNPs and related genes. We found that SNP rs4383 C>G was remarkably related with the reduced risk of bladder cancer (odds ratio = 0.68, 95% confidence interval = 0.59‐0.79, P = 3.91 × 10−7). Similar results were obtained in codominant, dominant and recessive model. Stratified analyses revealed that the effect of SNP rs4383 C>G on bladder cancer was more significant in the older subjects (age > 65), female and nonsmokers. sQTL analysis showed that SNP rs4383 was associated with the AS events of its downstream gene MAFF with a splicing event of alternative 5′ splice site. The messenger RNA expression of MAFF in bladder tumor tissues was lowered compared with normal tissues. Patients with high expression of MAFF had higher survival rates. These findings indicated that SNP rs4383 related with the AS events of MAFF was associated with bladder cancer risk and could represent a possible biomarker for bladder cancer susceptibility.

A Novel Prognostic and Predictive Signature for Lung Adenocarcinoma Derived from Combined Hypoxia and Infiltrating Immune Cell-Related Genes in TCGA Patients

“…MAFF is an important regulator of gene expression that participates in different pathophysiological processes including cancer development. 36 , 37 Indeed, we found that MAFF was downregulated in LUAD, similar to observations in other cancers including hepatocellular (HCC) and breast cancer. 37 As reported by Minhua et al, MAFF participates in HCC progression through the circ-ITCH/miR-224-5p/MAFF pathway.…”

Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

“…Detecting these AS events may, therefore, facilitate a better understanding of the functional specialization of cell types and tissues [ 7 ]. Researchers have suggested that AS events were associated with diseases, including a novel biomarker for predicting triple-negative breast cancer [ 8 ] and AS-associated genetic variants that increase the risks of bladder cancer in human [ 9 ]. Reproduction is a key process for the generation of offspring in mammals.…”

The underlying molecular mechanism and identification of transcription factor markers for laryngeal squamous cell carcinoma

“…Another PIRTF of LSCC, MAFF , has also been reported in several cancers other than LSCC. For example, bladder cancer patients with high MAFF expression have a higher survival rate [ 59 ], suggesting a cancer suppression effect, yet it remains controversial whether MAFF has a tumor suppressor effect in hepatocellular carcinoma. For example, Tsuchiya et al identified that knocking down MAFF expression would inhibit the invasion of hepatocellular carcinoma cells [ 60 ]; while Wu et al believed that MAFF exerts a tumor suppressor effect via the circ-ITCH/miR-224-5p axis in hepatocellular carcinoma [ 61 ].…”