Genetic variants in noncoding PIWI-interacting RNA and colorectal cancer risk.

CANCER(2015)

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摘要
BACKGROUNDPIWI-interacting RNAs (piRNAs), which are a novel type of identified small noncoding RNA (ncRNA), play a crucial role in germline development and carcinogenesis. METHODSBy systematically screening all known piRNAs, the authors identified 7 common single nucleotide polymorphisms (SNPs) in 9 piRNAs. Associations between these selected SNPs and the risk of colorectal cancer (CRC) were detected in a case-control study. A quantitative real-time polymerase chain reaction assay was used to evaluate messenger RNA (mRNA) expression levels of piR-015551 and of the long ncRNA (lncRNA) LNC00964-3 in 88 pairs of tissue samples. RESULTSThe assay revealed that reference SNP rs11776042 in piR-015551 was significantly associated with a decreased risk of CRC in an additive model (P=.020). However, this protective effect was not significant after correction for multiple comparisons (test for the false discovery rate; P=.140). Furthermore, the authors observed that mRNA expression levels of LNC00964-3 (an lncRNA that included the piR-015551 sequence but not piR-015551) were significantly lower in CRC tissues than in corresponding normal tissues (P=1.5 x 10(-5) for LNC00964-3; P=.899 for piR-015551). Correlation analysis revealed that piR-015551 expression was positively correlated with expression levels of LNC00964-3 (CRC tissues: r=0.574, P=5.13 x 10(-9); normal tissues: r=0.601, P=5.76 x 10(-10)). Moreover, rs11776042 was not significantly correlated with mRNA expression levels of piR-015551 or LNC00964-3 (all P>.05). CONCLUSIONSThe current findings reveal the possibility that piR-015551 may be generated from LNC00964-3, which may be involved in the development of CRC. Cancer 2015;121:2044-2052. (c) 2015 American Cancer Society. The PIWI-interacting RNA 015551 reference single nucleotide polymorphism rs11776042, which is located in the long noncoding RNA LNC00964-3, may decrease the risk of colorectal cancer, and the expression level of this interacting RNA has a positive correlation with that of LNC00964-3.
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关键词
colorectal cancer,genetic variation,long noncoding RNA,molecular epidemiology,PIWI-interacting RNA,susceptibility
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