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MicroRNA-940 restricts the expression of metastasis-associated gene MACC1 and enhances the antitumor effect of Anlotinib on colorectal cancer

Authors Wang Y, Zhao M, Zhao H, Cheng S, Bai R, Song M

Received 20 November 2018

Accepted for publication 28 February 2019

Published 12 April 2019 Volume 2019:12 Pages 2809—2822


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang

Yan Wang,1 Meng Zhao,2 Huishan Zhao,3 Shi Cheng,1 Rixing Bai,1 Maomin Song1

1Department of General Surgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Breast Surgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China

Background: Metastasis-associated with colon cancer-1 (MACC1) is an important regulator that promotes colorectal cancer (CRC) cells’ proliferation and distant metastasis. Therefore, MACC1 is considered as a promising therapeutic target of CRC. This work aimed to identify the microRNA (miR) targeted to MACC1, and to study the potential of using the particular miR in enhancing the antitumor effect of chemotherapy.
Materials and methods: miR prediction was performed in the miR database. The effect of miR-940 on MACC1’s expression was examined by Western blot, and the effect of miR-940 on the expression of genes related to the epithelial–mesenchymal transition (EMT) was identified by quantitative real-time polymerase chain reaction experiments. In vivo growth of CRC cells were analyzed in the nude mice subcutaneous tumor model and CRC liver metastasis model.
Results: By using the database, miR-940 was identified to target to the 3ʹUTR of MACC1’s mRNA. Experimentally, transfection of miR-940 decreased the expression of MACC1 in CRC cells and inhibited the EMT process of the transfected cells. MiR-940 also enhanced the inhibitory effect of Anlotinib on CRC cells’ in vivo growth and invasion. Correspondingly, ectopic expression of MACC1 mutant, which does not contain miR-940 binding site, blocked the antitumor effect of miR-940 on CRC cells.
Conclusion: MiR-940 restricts the proliferation and invasion of CRC cells by targeting to MACC1’s mRNA, and enhances the antitumor effect of Anlotinib on CRC tumors.

Keywords: colorectal cancer, Anlotinib, metastasis-associated gene in colon cancer 1, proliferation, in vivo invasive growth

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