A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients

Abstract

Abstract. MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3'UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088-5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3'UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients. IntroductionSmall cell lung cancer (SCLC), commonly classified by the Veterans Administration Lung Cancer Study Group as Limited stage and Extensive stage groups, constitutes ~15% of all lung cancer cases and is strongly associated with cigarette smoking (1-3). The prognosis of SCLC, which has been associated with extent of disease and other factors, is poor, whereas the life expectancy of those with untreated SCLC is ~3.5 months for the limited stage group and 6 weeks for the extensive stage group (4-6). Although genetic factors have been identified as prognostic factors for SCLC, the underlying mechanism of this cancer remains unknown (7-9).MicroRNAs (miRNAs) are RNA molecules that are ~22 nucleotides long and are involved in various biological processes, such as embryonic development, cell differentiation, proliferation, apoptosis, cancer development and insulin secretion (10,11). More than 700 miRNAs have been identified in humans and these miRNAs are responsible for regulating at least 30% of protein-coding gene expressions (12). A growing body of evidence suggests that miRNAs play important roles in a broad range of biological processes, as previously mentioned (9-11). In the miRNA processing, long primary transcripts of miRNAs (pri-miRNAs) are processed in the nucleus by RNase III Drosha and transported to the cytoplasm by the nuclear transport factor exportin-5 (XPO5) and RAN. In the cytoplasm, RNase III Dicer and transactivation-responsive RNA-binding protein (TRBP) mediate the processing of pre-miRNAs in order to release a 21-bp dsRNA. Additionally, the RNA-induced silencing complex (RISC) including GEMIN3 and GEMIN4 selects a single strand as the mature miRNA and guides the mature miRNAs to their target mRNA sites (10,13-16). miRNA-related single nucleotide polymorphisms (miR-SNPs), defined as SNPs in miRNA genes, miRNA binding site and miRNA processing machi...

Correlation of genetic polymorphism of vascular endothelial growth factor gene with susceptibility to lung cancer

“…For example, positive family history is an independent risk for this tumor, and recent studies have identified SNP polymorphisms in individual genes or micro RNAs associated with increased risk for this malignancy. [10][11][12][13][14][15][16] In the present study, we found that VEGF +405G/C SNP polymorphism is associated with risk of lung cancer. Consistent with results of previous clinical and experimental studies, our data also indicated that smoking is a risk factor for lung cancer, with a predilection in males.…”

Elevated XPO6 expression as a potential prognostic biomarker for prostate cancer recurrence

“…Dysregulation of XPOs associated with subcellular mislocalization of proteins has been reported for various types of human cancer (23). Upregulation of certain XPOs in particular has been associated with cancer progression (24)(25)(26)(27)(28)(29)(30)(31)(32)).…”

Single-Nucleotide Polymorphisms in XPO5 are Associated with Noise-Induced Hearing Loss in a Chinese Population

“…Previous results have indicated that overexpression of XPO5 enhances the activity of miRNAs, and under-or nonexpression of XPO5 results in a decrease in the nuclear output of pre-miRNAs [16,17]. SNPs associated with miRNAs in the XPO5 3′untranslated region (3′UTR) affect the risk of disease in the synthesis pathway of miRNAs [18]. Currently, there is a lack of research on the relationship betweenXPO5 and the risk of NIHL development; however, several studies have demonstrated that the transporter, XPO5, is involved in the miRNA pathway.…”