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

Cancer. 2015 Jun 15;121(12):2044-52. doi: 10.1002/cncr.29314. Epub 2015 Mar 4.

Abstract

Background: PIWI-interacting RNAs (piRNAs), which are a novel type of identified small noncoding RNA (ncRNA), play a crucial role in germline development and carcinogenesis.

Methods: By 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.

Results: The 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 × 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 × 10(-9) ; normal tissues: r = 0.601, P = 5.76 × 10(-10)). Moreover, rs11776042 was not significantly correlated with mRNA expression levels of piR-015551 or LNC00964-3 (all P > .05).

Conclusions: The current findings reveal the possibility that piR-015551 may be generated from LNC00964-3, which may be involved in the development of CRC.

Keywords: PIWI-interacting RNA; colorectal cancer; genetic variation; long noncoding RNA; molecular epidemiology; susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding