Oncotarget

Research Papers:

microRNA-210-3p depletion by CRISPR/Cas9 promoted tumorigenesis through revival of TWIST1 in renal cell carcinoma

Hirofumi Yoshino, Masaya Yonemori, Kazutaka Miyamoto, Syuichi Tatarano, Satoshi Kofuji, Nijiro Nohata, Masayuki Nakagawa and Hideki Enokida _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:20881-20894. https://doi.org/10.18632/oncotarget.14930

Metrics: HTML 1176 views  |   ?  


Abstract

Hirofumi Yoshino1, Masaya Yonemori1, Kazutaka Miyamoto1, Syuichi Tatarano1, Satoshi Kofuji2, Nijiro Nohata3, Masayuki Nakagawa1, Hideki Enokida1

1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan

2Department of Internal Medicine, Vontz Center, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0508, USA

3Moores UCSD Cancer Center, La Jolla, CA 92093-0803, USA

Correspondence to:

Hideki Enokida, email: enokida@m.kufm.kagoshima-u.ac.jp

Keywords: microRNA, miR-210-3p, renal cell carcinoma, CRISPR/Cas9, TWIST1

Received: September 20, 2016    Accepted: December 05, 2016    Published: February 01, 2017

ABSTRACT

Previous studies showed that five miRNAs (miR-885-5p, miR-1274, miR-210-3p, miR-224 and miR-1290) were upregulated the most in clear cell renal cell carcinoma (ccRCC). Our focus was to understand from a clinical standpoint the functional consequences of upregulating miR-210-3p. Towards this, we utilized the CRISPR/Cas9 gene editing system to deplete miR-210-3p in RCC cell lines (786-o, A498 and Caki2) and characterized the outcomes. We observed that miR-210-3p depletion dramatically increased tumorigenesis, including altering the morphology of A498 and Caki2 cells in a manner characteristic of epithelial-mesenchymal transition (EMT). These results were corroborated by in vivo xenograft studies, which showed enhanced growth of tumors from miR-210-3p-depleted A498 cells. We identified Twist-related protein 1 (TWIST1) as a key target of miR-210-3p. Analysis of the ccRCC patient data in The Cancer Genome Atlas database showed a negative correlation between miR-210-3p and TWIST1 expression. High TWIST1 and low miR-210-3p expression associated with poorer overall and disease-free survival as compared to low TWIST1 and high miR-210-3p expression. These findings suggest that renal cell carcinoma progression is promoted by TWIST1 suppression mediated by miR-210-3p.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14930