机构：[1]Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China[2]Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China[3]Department of Gastroenterology, the People's Hospital of Sihong County, Sihong, China[4]Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, China[5]Department of Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China[6]Department of Pathology, the Second Affiliated Hospital of Soochow University, Suzhou, China[7]Suzhou Key Laboratory of Tumor Microenvironment and Pathology, Soochow University, Suzhou, China
MicroRNAs, which regulate mRNAs, operate through a variety of signaling pathways to participate in the development of colorectal cancer (CRC). In this study, we found that microRNA (miR)-143-3p expression was significantly lower in both CRC and liver metastatic CRC tissues from liver compared with normal colonic tissues. Functional assays showed that miR-143-3p inhibited CRC cell invasion and migration in vitro. Using a bioinformatics approach, we identified miR-143-3p target mRNAs. Among the candidate targets, only the expression of integrin alpha 6 (ITGA6) and ArfGAP with the SH3 domain and ankyrin repeat and PH domain 3 (ASAP3) were significantly reduced by miR-143-3p mimics as examined by western blot, and the metastasis potential of CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown, determined by migration and invasion assays. Both ITGA6 and ASAP3 were upregulated in CRC tissues compared to normal tissues. Analysis of the relationship between clinicopathological features and ITGA6/ASAP3 protein expression in 200 patients with CRC showed a significant difference in positive ITGA6 expression between the early stage (I + II) and the advanced stage (III + IV), and ASAP3 expression levels positively correlated with metastasis in the lymph nodes. These results indicate that miR-143-3p acts as an anti-oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.
基金：
National Natural Science Foundation of China [81472297]; Priority Academic Program Development of Jiangsu Higher Education Institutions
第一作者机构：[1]Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
通讯作者：
通讯机构：[*1]Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
推荐引用方式(GB/T 7714)：
Lingchuan Guo,Jianhong Fu,Shimei Sun,et al.MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3[J].CANCER SCIENCE.2019,110(2):805-816.doi:10.1111/cas.13910.
APA：
Lingchuan Guo,Jianhong Fu,Shimei Sun,Minsheng Zhu,Lifeng Zhang...&Shouli Wang.(2019).MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3.CANCER SCIENCE,110,(2)
MLA：
Lingchuan Guo,et al."MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3".CANCER SCIENCE 110..2(2019):805-816
医学