MicroRNA‐143‐3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3

• Published in: Cancer science Vol. 110; no. 2; pp. 805 - 816
• Main Authors: Guo, Lingchuan, Fu, Jianhong, Sun, Shimei, Zhu, Minsheng, Zhang, Lifeng, Niu, Hui, Chen, Zhi, Zhang, Yongsheng, Guo, Lingling, Wang, Shouli
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2019; John Wiley and Sons Inc
• Subjects: Aged; Ankyrins; ASAP3; Bioinformatics; Cancer therapies; Cell adhesion & migration; Cell culture; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Down-Regulation - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; GTPase-Activating Proteins - genetics; HCT116 Cells; Humans; Integrin alpha6 - genetics; ITGA6; Liver; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Male; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; miRNA; miR‐143‐3p; Original; Prostate cancer; RNA, Messenger - genetics; Signal Transduction - genetics; Therapeutic applications; Tumors; Up-Regulation - genetics; United States > US; China; miR-143-3p; ASAP3; ITGA6; colorectal cancer; metastasis
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13910

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. We detected a more significant decrease in microRNA (miR)‐143‐3p expression levels in clinical specimens of colorectal cancer than that in normal tissues, and showed that miR‐143‐3p‐mimics inhibit the invasion and migration of CRC cells in vitro. Using a bioinformatics approach and functional assays, we identified ITGA6 and ASAP3 as the target genes of miR‐143‐3p, and the metastatic potential of the CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown.