Abstract 517: MiR-29b is a novel potential prognostic marker and inhibits cell proliferation in colorectal cancer

Abstract

Abstract Introduction Accumulating evidence indicates that microRNAs (miRNAs) are aberrantly expressed in human cancers and contribute to the tumorigenesis. Recent studies have suggested that microRNA-29 (miR-29) family members in human may play an important role in many types of cancer by regulating cell proliferation, differentiation, apoptosis, migration and invasion. MiR-29 is considered good candidate for miRNA-based therapeutics. In colorectal cancer (CRC), however, few studies have shown the clinical significance and biological function of miR-29. The aim of the present study was to examine the prognostic impact of miR-29b and the biological significance of miR-29b in CRC. Materials and methods Expression of miR-29b was quantified by quantitative real-time PCR in 127 CRC patients who underwent curative resection. The impact of miR-29b expression on disease free survival (DFS) and overall survival (OS) was assessed in these 127 CRC patients. To investigate the functional role of miR-29b in vitro, tumor suppressive activity of miR-29b was assessed by proliferation assay, TUNEL assay and Ki-67 staining in CRC-derived cell lines (DLD1, HT29 and SW480). Results MiR-29b expression was significantly decreased in tumor tissues compared to corresponding normal tissue (P = 0.014). The DFS and OS were significantly longer in the high miR-29b expression group compared to those in the low miR-29b expression group (P < 0.05). Univariate and multivariate analyses indicated that expression of miR-29b was an independent prognostic factor for OS (P = 0.003), together with lymph node metastasis (P = 0.009), and serosal invasion (P = 0.002). In vitro assays revealed that forced expression of miR-29b was associated with a reduction of proliferative activity. TUNEL assay and Ki-67 staining revealed that miR-29b could induce apoptosis and cell cycle arrest in CRC cell lines. Conclusions Our findings suggested that miR-29b is a useful prognostic marker for CRC, and could be a promising therapeutic target against CRC. Citation Format: Akira Inoue, Hirofumi Yamamoto, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori. MiR-29b is a novel potential prognostic marker and inhibits cell proliferation in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 517. doi:10.1158/1538-7445.AM2014-517