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Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer.

ABSTRACT: Exportin 5 (XPO5) is a microRNA (miRNA)-related nuclear export protein, and its disorder may lead to the dysregulation of miRNAs. Recent studies have demonstrated that the aberrant expression of XPO5 might participate in carcinogenesis in certain cancers. However, there is only limited information of XPO5 in thyroid cancer (TC) development. In our study, we quantified the expression level of XPO5 by real-time polymerase chain reaction (PCR) in 64 TC patients' cancer tissues and adjacent normal tissues. After confirming the XPO5 expression, we evaluated the association between XPO5 potential functional single-nucleotide polymorphisms (SNPs) and risk of TC in a Chinese population (1140 cases vs 1230 controls). Finally, luciferase assays were performed to investigate the function of the SNP in XPO5 3' untranslation region. The message ribonucleic acid (RNA) levels of XPO5 were significantly lower in cancer tissues than normal tissues (P?=?0.004). In SNPs screening, only 1 noble SNP rs11077 was identified in XPO5 functional region. The results in our case-control study also confirmed that XPO5 rs11077 was significantly associated with onset of TC (GT/GG vs TT P?=?0.035, adjusted odds ratio?=?1.25, 95% confidence interval?=?1.02-1.54). The adverse influence of this polymorphism was mainly observed in age >45 years (P?=?0.028), female (P?=?0.020), T1 staging (P?=?0.026), N1 (P?=?0.038), metastasis (P?=?0.031 M0, and P?=?0.035 for M1), and early stage (I?+?II) (P?=?0.021). A following luciferase test revealed the critical role of rs11077 for triggering the XPO5 expression. Furthermore, patients with G allele of rs11077 showed lower XPO5 expression level. XPO5 SNP rs11077 influences the expression of XPO5, and this SNP could also be a potential biomarker for the diagnosis of TC in clinical, especially in Chinese population.

SUBMITTER: Wen J

PROVIDER: S-EPMC5411189 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer.

Wen Jing J Gao Qingjun Q Wang Nanpeng N Zhang Wei W Cao Kun K Zhang Qiang Q Chen Shi S Shi Lixin L

Medicine 20170401 14

Exportin 5 (XPO5) is a microRNA (miRNA)-related nuclear export protein, and its disorder may lead to the dysregulation of miRNAs. Recent studies have demonstrated that the aberrant expression of XPO5 might participate in carcinogenesis in certain cancers. However, there is only limited information of XPO5 in thyroid cancer (TC) development. In our study, we quantified the expression level of XPO5 by real-time polymerase chain reaction (PCR) in 64 TC patients' cancer tissues and adjacent normal t ...[more]

PMID: 28383405

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Project description:OBJECTIVES:Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, which accounts for 80-90% of all thyroid cancer cases. Though the pathological mechanism hasn't been fully understood, it is reported that both environmental and genetic factor may contribute to the PTC susceptibility. MicroRNAs (miRNAs) are small non-coding RNA molecules which function as the suppressors to participate in a variety of biological processes. Accumulating evidence suggests that polymorphisms of miRNAs were associated with the tumorigenesis of various cancers, including PTC. In this article, we focus on the association between four common microRNA polymorphisms (miR-146a, miR-608, miR-933, and miR-149) and PTC risk in a Han Chinese population. METHODS:In this case-control study, we recruited 1,398 participants in total, including 369 PTC patients, 278 patients with thyroid benign nodules (BN) and 751 normal controls. The miRNAs polymorphisms were genotyped and analyzed by using MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were calculated to evaluate the association between miRNAs polymorphisms and PTC risk. Furthermore, a meta-analysis based on previous studies was conducted to comprehensively assess the diagnostic performance of miR-146a in the PTC diagnosis. RESULTS:The miR-146a polymorphisms were shown to be significantly correlated with elevated risk of PTC under the heterozygous, homozygous, dominant and allelic models by comparing the genotype distribution between PTC cases and healthy controls, as well as between PTC cases and BN cases. However, the result of meta-analysis showed no significant association between miR-146a polymorphisms and PTC risk. CONCLUSIONS:Our study indicated that the miR-146a polymorphism was significantly associated with PTC risk. In contrast, meta-analysis revealed no evidence of association between miR-146a variants and PTC risk. Further studies are required to elucidate the role of miR-146a in the etiology of PTC.

Dataset Information

Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer.

Publications

Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer.

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