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microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer

Authors :
Kota Ouchi
Michiaki Unno
Chikashi Ishioka
Yasuhide Yamada
Shin Takahashi
Yuki Yoshino
Hidekazu Takahashi
Masanobu Takahashi
Shinobu Ohnuma
Hideki Shimodaira
Source :
BMC Cancer, Vol 17, Iss 1, Pp 1-14 (2017), BMC Cancer
Publication Year :
2017
Publisher :
Springer Science and Business Media LLC, 2017.

Abstract

Background The aim of this study was to identify miRNAs specifically dysregulated in BRAF-mutated colorectal cancer, which could lead to a better understanding of the molecular mechanisms underlying oncogenesis of this malignant subtype of colorectal cancer. Methods Candidate dysregulated miRNAs were selected in genome-wide miRNA expression array analysis using a screening set composed of 15 BRAF-mutated and 15 non-KRAS/BRAF-mutated colorectal cancers. The miRNA expressions were validated in another set of patients. The functional roles of the miRNAs were analyzed by cell growth and invasion assays. The association between miRNA expression status and the clinical outcome of patients treated with various chemotherapies was analyzed. Results Within the top five of the miRNAs screened, we validated miRNA-31 (miR-31) and miR-135b as up-regulated, while miR-193a-3p was down-regulated in BRAF-mutated cancer. Moreover, miR-193a-3p inhibited cell growth, and invasion of colorectal cancer cells. Low miR-193a-3p expression was associated with shorter progression-free survival in patients who received anti-EGFR therapy. Conclusions Our results disclose a novel tumor suppressive role of miR-193a-3p in colorectal cancer. These results could lead to novel therapeutic strategies for colorectal cancer, particularly in BRAF-mutated colorectal cancer. Electronic supplementary material The online version of this article (10.1186/s12885-017-3739-x) contains supplementary material, which is available to authorized users.

Details

ISSN :
14712407
Volume :
17
Database :
OpenAIRE
Journal :
BMC Cancer
Accession number :
edsair.doi.dedup.....93c57324e8cda06757fafaa81dccd205
Full Text :
https://doi.org/10.1186/s12885-017-3739-x