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lncRNA LINC00460 promoted colorectal cancer cells metastasis via miR-939-5p sponging

Authors Zhang Y, Liu XC, Li Q, Zhang Y

Received 27 October 2018

Accepted for publication 17 December 2018

Published 22 February 2019 Volume 2019:11 Pages 1779—1789

DOI https://doi.org/10.2147/CMAR.S192452

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yueyan Zhang,1* Xingchi Liu,2* Qiang Li,1* Yong Zhang1

1Department of Pathology, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Thoracic Surgery, General Hospital of Shenyang Military Command, Shenyang, People’s Republic of China

*These authors contributed equally to this work

Background: lncRNAs are widely involved in multiple malignancies including colorectal cancer (CRC). The expression and function of long intergenic non-protein coding RNA 460 (LINC00460) in CRC remains obscure.
Methods: In the present study, quantitative real-time PCR assays were applied to detect the expression changes of LINC00460 and microRNA-939-5p (miR-939-5p) in CRC tissue specimens and cell lines. Western blot assays were used to measure the changes of LIMK2. Bioinformatics analysis, luciferase assays, and RNA pull-down assays were applied to determine the targeting binding effect between LINC00460 and miR-939-5p as well as LIMK2 and miR-939-5p. Transwell assays were used to evaluate the metastatic ability changes of CRC line HT29 and LOVO cells.
Results: We found that LINC00460 was upregulated and closely correlated to clinicopathological features and poor prognosis of patients with CRC. Functionally, we elucidated that LINC00460 promoted metastasis in CRC cell lines HT29 and LOVO. Further, we showed that LIMK2 was a downstream effector in the LINC00460-induced promotion of metastasis in CRC cells HT29 and LOVO. Through online bioinformatics analysis, LINC00460 and LIMK2 were demonstrated to share similar microRNA response elements for miR-939-5p. Then, LINC00460 and LIMK2 were verified to be the targets of miR-939-5p via a luciferase assay and an RNA pull-down assay. Also, miR-939-5p was showed to suppress metastasis by targeting of LIMK2. Lastly, we revealed that LINC00460 promoted LIMK2-mediated metastasis via miR-939-5p sponging in CRC cells HT29 and LOVO.
Conclusion: The findings of this study showed that LINC00460 works as an oncogene in CRC and promoted CRC cell metastasis via regulation of miR-939-3p/LIMK2 axial. The present study might provide a new target in treating CRC.

Keywords: LINC00460, miR-939-5p, ceRNA, metastasis, colorectal cancer

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