Small RNA Profiling of piRNAs in Colorectal Cancer Identifies Consistent Overexpression of piR-24000 That Correlates Clinically with an Aggressive Disease Phenotype

Abstract

Piwi-interacting RNAs (piRNAs) represent a novel class of small non-coding RNAs (ncRNAs) that have been shown to have a deregulated expression in several cancers, although their clinical significance in colorectal cancer (CRC) remains unclear. With an aim of delineating the piRNA distribution in CRC, we conducted a systematic discovery and validation of piRNAs within two clinical cohorts. In the discovery phase, we profiled tumor and adjacent normal tissues from 18 CRC patients by deep sequencing and identified a global piRNA downregulation in CRC. Moreover, we identified <i>piR-24000</i> as an unexplored piRNA that was significantly overexpressed in CRC. Using qPCR, we validated the overexpression of <i>piR-24000</i> in 87 CRC patients. Additionally, we identified a significant association between a high expression of <i>piR-24000</i> and an aggressive CRC phenotype including poor differentiation, presence of distant metastases, and a higher stage. Lastly, ROC analysis demonstrated a strong diagnostic power of <i>piR-24000</i> in discriminating CRC patients from normal subjects. Taken together, this study provides one of the earliest large-scale reports of the global distribution of piRNAs in CRC. In addition, <i>piR-24000</i> was identified as a likely oncogene in CRC that can serve as a biomarker or a therapeutic target.