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A genetic variant of miR-148a binding site in the SCRN1 3 ′ -UTR is associated with susceptibility and prognosis of gastric cancer

View Article: PubMed Central - PubMed

ABSTRACT

Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions targeted by putative mircoRNA can change its binding strength, affecting the susceptibility and prognosis of cancer. We aimed to investigate the associations between SNPs within miR-148a binding sites and gastric cancer (GC) risk and prognosis. Using bioinformatics tools, we selected two SNPs (SCRN1 rs6976789 and PDYN rs2235749) located in miR-148a target sites. We genotyped the two SNPs in a case-control study comprising 753 GC patients and 949 cancer-free subjects. We found a significantly increased risk of GC associated with the SCRN1 rs6976789 C>T polymorphism [adjusted OR = 1.25, 95% confidence interval (CI) = 1.02–1.53; CT/TT vs. CC]. However, no significant association was found between the PDYN rs2235749 and GC risk in all genetic models. Furthermore, we evaluated whether SCRN1 rs6976789 affected the survival of GC patients. Results showed that individuals with SCRN1 rs6976789 TT genotype had poorer overall survival compared with those carried CC/CT genotypes in intestinal-type GC (adjusted HR = 2.47, 95% CI = 1.21–5.05). Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Our results suggested that the SCRN1 rs6976789 polymorphism may play an important role in the GC development and progression.

No MeSH data available.


Related in: MedlinePlus

Effect of the miR-148a and SNP rs6976789 on the expression of SCRN1 in gastric cancer.Relative expression levels of (A) SCRN1 mRNA and (B) miR-148a were detected in 32 pairs of human gastric cancer tissues and adjacent normal tissues via qRT-PCR. Abundance of and SCRN1 mRNA and miRNA was normalized to GAPDH and U6 RNA, respectively. (C) Spearman's correlation analysis of SCRN1 mRNA expression levels to miR-148a in 32 gastric cancer tissues. (D) Association between rs6976789 polymorphism and SCRN1 mRNA levels in gastric cancer cases.
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f3: Effect of the miR-148a and SNP rs6976789 on the expression of SCRN1 in gastric cancer.Relative expression levels of (A) SCRN1 mRNA and (B) miR-148a were detected in 32 pairs of human gastric cancer tissues and adjacent normal tissues via qRT-PCR. Abundance of and SCRN1 mRNA and miRNA was normalized to GAPDH and U6 RNA, respectively. (C) Spearman's correlation analysis of SCRN1 mRNA expression levels to miR-148a in 32 gastric cancer tissues. (D) Association between rs6976789 polymorphism and SCRN1 mRNA levels in gastric cancer cases.

Mentions: To determine the expression of SCRN1 and miR-148a in GC and correlate their expression to the different genotypes of the SNP rs6976789, we employed RT-PCR in 32 pairs of GC and non-GC sample. As shown in Fig. 3A, SCRN1 mRNA expression levels were significantly up-regulated in gastric carcinoma relative to adjacent normal mucosae. On the contrary, miR-148a was significantly down-regulated in GC tissues (Fig. 3B). A significant reverse correlation between miR-148a and SCRN1 mRNA expression was identified in 32 GC tissues (r = −0.427, P = 0.015, Fig. 3C). We further evaluated whether the rs6976789 polymorphism could influence SCRN1expression in GC. Our results showed that the C to T polymorphism did not change the expression level. The expression levels of SCRN1 in individuals with CT carriers (P = 0.298) or CT/TT carriers (P = 0.461) have no significant difference with those with CC carriers (Fig. 3D). Additionally, the expression levels of miR-148a were no obvious different in patients with or without variant allele (Supplementary Fig. S1).


A genetic variant of miR-148a binding site in the SCRN1 3 ′ -UTR is associated with susceptibility and prognosis of gastric cancer
Effect of the miR-148a and SNP rs6976789 on the expression of SCRN1 in gastric cancer.Relative expression levels of (A) SCRN1 mRNA and (B) miR-148a were detected in 32 pairs of human gastric cancer tissues and adjacent normal tissues via qRT-PCR. Abundance of and SCRN1 mRNA and miRNA was normalized to GAPDH and U6 RNA, respectively. (C) Spearman's correlation analysis of SCRN1 mRNA expression levels to miR-148a in 32 gastric cancer tissues. (D) Association between rs6976789 polymorphism and SCRN1 mRNA levels in gastric cancer cases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382666&req=5

f3: Effect of the miR-148a and SNP rs6976789 on the expression of SCRN1 in gastric cancer.Relative expression levels of (A) SCRN1 mRNA and (B) miR-148a were detected in 32 pairs of human gastric cancer tissues and adjacent normal tissues via qRT-PCR. Abundance of and SCRN1 mRNA and miRNA was normalized to GAPDH and U6 RNA, respectively. (C) Spearman's correlation analysis of SCRN1 mRNA expression levels to miR-148a in 32 gastric cancer tissues. (D) Association between rs6976789 polymorphism and SCRN1 mRNA levels in gastric cancer cases.
Mentions: To determine the expression of SCRN1 and miR-148a in GC and correlate their expression to the different genotypes of the SNP rs6976789, we employed RT-PCR in 32 pairs of GC and non-GC sample. As shown in Fig. 3A, SCRN1 mRNA expression levels were significantly up-regulated in gastric carcinoma relative to adjacent normal mucosae. On the contrary, miR-148a was significantly down-regulated in GC tissues (Fig. 3B). A significant reverse correlation between miR-148a and SCRN1 mRNA expression was identified in 32 GC tissues (r = −0.427, P = 0.015, Fig. 3C). We further evaluated whether the rs6976789 polymorphism could influence SCRN1expression in GC. Our results showed that the C to T polymorphism did not change the expression level. The expression levels of SCRN1 in individuals with CT carriers (P = 0.298) or CT/TT carriers (P = 0.461) have no significant difference with those with CC carriers (Fig. 3D). Additionally, the expression levels of miR-148a were no obvious different in patients with or without variant allele (Supplementary Fig. S1).

View Article: PubMed Central - PubMed

ABSTRACT

Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions targeted by putative mircoRNA can change its binding strength, affecting the susceptibility and prognosis of cancer. We aimed to investigate the associations between SNPs within miR-148a binding sites and gastric cancer (GC) risk and prognosis. Using bioinformatics tools, we selected two SNPs (SCRN1 rs6976789 and PDYN rs2235749) located in miR-148a target sites. We genotyped the two SNPs in a case-control study comprising 753 GC patients and 949 cancer-free subjects. We found a significantly increased risk of GC associated with the SCRN1 rs6976789 C>T polymorphism [adjusted OR = 1.25, 95% confidence interval (CI) = 1.02–1.53; CT/TT vs. CC]. However, no significant association was found between the PDYN rs2235749 and GC risk in all genetic models. Furthermore, we evaluated whether SCRN1 rs6976789 affected the survival of GC patients. Results showed that individuals with SCRN1 rs6976789 TT genotype had poorer overall survival compared with those carried CC/CT genotypes in intestinal-type GC (adjusted HR = 2.47, 95% CI = 1.21–5.05). Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Our results suggested that the SCRN1 rs6976789 polymorphism may play an important role in the GC development and progression.

No MeSH data available.


Related in: MedlinePlus