Abstract 5244: MicorRNA-27a functions as a tumor suppressor in colorectal cancer through targeting SPGG1 and Smad2

Abstract

Abstract Colorectal cancer is one of the most common malignant diseases worldwide, but the causes of colorectal carcinogenesis are largely unknown. Using a miRNA array we have identified differential expression of some microRNAs in colorectal cancer and adjacent normal mucosa. Most of these miRNAs have been validated in colorectal tissues by quantitative RT-PCR. One of the most changed miRNAs is miR-27a. The level of miR-27 was significantly reduced in colon cancers in compared with matched normal mucosa, the reduced expression of miR-27a was also associated with colorectal cancer pathological stages - miR-27a was more reduced at stages III/IV, compared to stage II. The levels of miR-27a in human colon cancer cell lines were also less than that in human normal colon epithelial cell lines. Using bioinformatic and systemic analysis, two targets of miR-27a were predicted, they were SPGG1 and Smad2. The expression levels of SPGG1 and Smad2 were negatively correlated with miR-27a. Dual luciferase assay showed that overexpression of miR-27 significantly repressed SPGG1 and Smad2 transcriptional activities. Increasing miR-27 expression also inhibited SPGG1 and Smad2 protein levels in colon cancer cells. Functional studies revealed that overexpression of miR-27 inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were linked to downregulation of p-STAT3 and upregulation of phosphorylated JNK1. Taken together, our results demonstrated that the expression levels of miR-27a were lower in colorectal cancer tissues in comparison to the non-tumor tissues and was related to pathological stages, suggesting that down-regulation of this miRNA could contribute to colorectal tumorigenesis and the acquisition of a more aggressive phenotype in colorectal cancer, which could be through targeting SPGG1 and Smad2. Note: This abstract was not presented at the meeting. Citation Format: Yonghua Bao, Zhiguo Chen, Yongchen Guo, Tiesuo Zhao, Yansheng Feng, Yunjuan Jiao, Zexin Li, Jianguo Wang, Weixing Zhao, Kai Li, Qian Wang, Jiaqi Wang, Huijuan Zhang, Wancai Yang, Wancai Yang. MicorRNA-27a functions as a tumor suppressor in colorectal cancer through targeting SPGG1 and Smad2. [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 5244. doi:10.1158/1538-7445.AM2014-5244