TY - JOUR
T1 - Circular RNA ciRS-7 — A promising prognostic biomarker and a potential therapeutic target in colorectal cancer
AU - Weng, Wenhao
AU - Wei, Qing
AU - Toden, Shusuke
AU - Yoshida, Kazuhiro
AU - Nagasaka, Takeshi
AU - Fujiwara, Toshiyoshi
AU - Cai, Sanjun
AU - Qin, Huanlong
AU - Ma, Yanlei
AU - Goel, Ajay
N1 - Funding Information:
The authors thank Dr. Thomas B. Hansen for providing plasmids and invaluable suggestions and guidance of this project. This work was supported by the grants R01 CA72851, CA181572, CA184792, and U01 CA187956 from the National Cancer Institute, NIH, pilot grants from the Baylor Sammons Cancer Center and Foundation, as well as funds from the Baylor Research Institute. In addition, the current work was supported by the grants from the National Natural Science Foundation of China (no. 81372615), and the Shanghai Health System Outstanding Young Talent Training Plan (no. XYQ2013118). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2017 AACR.
PY - 2017/7/15
Y1 - 2017/7/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-16-2541
DO - 10.1158/1078-0432.CCR-16-2541
M3 - Article
C2 - 28174233
AN - SCOPUS:85022031004
VL - 23
SP - 3918
EP - 3928
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 14
ER -