The aim of this study was to identify microRNAs (miRNAs) specifically dysregulated in BRAF-mutant colorectal cancer, a malignant subtype of colorectal cancer. The genome-wide miRNA expression analysis in a screening set (n = 30) identified 22 miRNAs specifically dysregulated in BRAF-mutant cancers. Among the top 5 dysregulated miRNAs, the validation analysis using another set of patients (n = 34) confirmed miR-31 and miR-135b as significantly up-regulated miRNAs and miR-193a-3p as a significantly down-regulated one. Moreover, functional assays supported its tumor-suppressive role in colorectal cancer. Finally, the expression status of miR-193a-3p correlated with clinical outcome of patients treated with anti-EGFR antibodies. Taken together, these results show a novel functional role of miR-193a-3p as a tumor suppressive miRNA in colorectal cancer, particularly with BRAF mutations. Further studies are needed to clarify the precise molecular mechanisms as to how this miRNA is involved in colorectal tumorigenesis, which could help further develop a therapeutic strategy for colorectal cancer.
Citation Format: Hidekazu Takahashi, Masanobu Takahashi, Shin Takahashi, Hideki Shimodaira, Chikashi Ishioka. microRNA-193a-3p acts as a tumor suppressor in BRAF-mutated colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1096.