Circular RNA ciRS-7 — A promising prognostic biomarker and a potential therapeutic target in colorectal cancer

Wenhao Weng, Qing Wei, Shusuke Toden, Kazuhiro Yoshida, Takeshi Nagasaka, Toshiyoshi Fujiwara, Sanjun Cai, Huanlong Qin, Yanlei Ma, Ajay Goel

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Purpose: Colorectal cancer is one of themost common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients. Experimental Design: Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (n = 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings. Results: Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (P = 0.0018), and its overexpression was associated with poor patient survival (P = 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (P = 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes. Conclusions: CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients.

Original languageEnglish
Pages (from-to)3918-3928
Number of pages11
JournalClinical Cancer Research
Volume23
Issue number14
DOIs
Publication statusPublished - Jul 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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