Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer

Wenhao Weng, Na Liu, Yuji Toiyama, Masato Kusunoki, Takeshi Nagasaka, Toshiyoshi Fujiwara, Qing Wei, Huanlong Qin, Haifan Lin, Yanlei Ma, Ajay Goel

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24 Citations (Scopus)

Abstract

Background: Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may be important epigenetic regulators of gene expression in human cancers; however, their functional and clinical significance in colorectal cancer (CRC) remains unknown. Methods: We performed piRNA expression profiling in paired cancer and normal tissues through small RNA-sequencing. The clinical significance of candidate piRNAs was investigated, and independently validated in 771 CRC patients from three independent cohorts. The biological function of piRNAs was characterized in cell lines, followed by identification and validation of downstream target genes in CRC tissues. Results: We identified piR-1245 as a novel and frequently overexpressed noncoding RNA in CRC, and its expression significantly correlated with advanced and metastatic disease. Patients with high piR-1245 expression experienced significantly shorter overall survival, and multivariate analysis identified its expression to serve as an independent prognostic biomarker in CRC. Functionally, piR-1245 acts as an oncogene and promotes tumor progression, and gene expression profiling results identified a panel of downstream target-genes involved in regulating cell survival pathway. Based upon piRNA:mRNA sequence complementarity, we identified a panel of tumor suppressor genes (ATF3, BTG1, DUSP1, FAS,NFKBIA, UPP1, SESN2, TP53INP1 and MDX1) as direct targets of piR-1245, and successfully validated an inverse correlation between their expression and piR-1245 in CRC. Conclusions: We for the first time have identified the role for a PIWI-interacting noncoding RNA, piR-1245, as a novel oncogene and a potential prognostic biomarker in colorectal cancer.

Original languageEnglish
Article number16
JournalMolecular Cancer
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 30 2018

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Keywords

  • Biomarker
  • Colorectal cancer
  • Noncoding RNA
  • Oncogene
  • PiR-1245
  • PiRNA
  • Prognosis
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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