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miR-665 Suppresses the Epithelial–Mesenchymal Transition and Progression of Gastric Cancer by Targeting CRIM1

Authors Wu KZ, Zhang CD, Zhang C, Pei JP, Dai DQ

Received 11 December 2019

Accepted for publication 21 April 2020

Published 15 May 2020 Volume 2020:12 Pages 3489—3501


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Seema Singh

Kun-Zhe Wu,1 Chun-Dong Zhang,1,2 Cheng Zhang,1 Jun-Peng Pei,1 Dong-Qiu Dai1,3

1Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, People’s Republic of China; 2Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Kashiwa 277-8561, Japan; 3Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, People’s Republic of China

Correspondence: Dong-Qiu Dai
Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road, Shenyang, Liaoning 110000, People’s Republic of China
Tel +86 159 0983 5960
Fax +86 24 6204 3110

Background: Gastric cancer (GC) is one of the most common aggressive cancers and is characterized by high mortality. Increasing evidence has shown that microRNA-665 (miRNA-665) serves as inhibiting-miRNA in cancers. However, the role of miR-665 in GC is yet unclear.
Methods: miR-665 was first analyzed using bioinformatics. Subsequent quantitative real-time PCR was used to detect miR-665 expression levels in different GC cell lines and tissues. The function of miR-665 in GC cells was determined via Cell Counting Kit 8, colony formation, wound healing, and transwell assays. Furthermore, Western blotting was utilized to measure the expression level of epithelial–mesenchymal transition (EMT)-related proteins. The target prediction and luciferase reporter assays were performed to confirm the binding between miR-665 and 3ʹ-UTR of the CRIM1 gene. In addition, rescue assays were used to determine whether CRIM1 upregulation abolished the inhibitory effect of miR-665.
Results: The expression of miR-665 was significantly decreased in GC patients and GC cell lines. Clinical and pathological analyses showed that the low expression of miR-665 was significantly associated with high TNM stage (P = 0.007), distant metastasis (P = 0.031), and poor differentiation (P = 0.029). Endogenic mimics of miR-665 remarkably suppressed GC cell proliferation, migration, invasion, and EMT in in vitro experiments. Inhibition of miR-665 expression induced the opposite effects. The results of the bioinformatics analysis and dual-luciferase assay showed that miR-665 targeted the 3ʹ-UTR of the CRIM1 gene. Rescue assays revealed that overexpression of CRIM1 attenuated the inhibitory effects of miR-665 in GC progression and EMT.
Conclusion: The overall study results demonstrated that miR-665 inhibits tumor progression and EMT in GC by targeting CRIM1, indicating that miR-665 might be a potential therapeutic target in the treatment of GC patients.

Keywords: gastric cancer, prognosis, miR-665, CRIM1, epithelial–mesenchymal transition

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