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Long non-coding RNA TUG1-mediated down-regulation of KLF4 contributes to metastasis and the epithelial-to-mesenchymal transition of colorectal cancer by miR-153-1

Authors Shao H, Dong D, Shao F

Received 12 March 2019

Accepted for publication 19 July 2019

Published 24 September 2019 Volume 2019:11 Pages 8699—8710

DOI https://doi.org/10.2147/CMAR.S208508

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


Hongjin Shao,1 Dianbo Dong,1 Feng Shao2

1Department of Proctology, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, People’s Republic of China; 2Department of Gastrointestinal Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, People’s Republic of China

Correspondence: Feng Shao
Department of Gastrointestinal Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, People’s Republic of China
Tel +86 1 396 956 7952
Email Shaofeng7952@126.com

Introduction: Taurine up-regulated 1 (TUG1) was reported to be over-expressed and involved in various human malignancies. However, its expression status and mechanistic importance in colorectal cancer (CRC) were yet to be defined.
Methods: Relative expressions of TUG1, miR-153-1 and Kruppel-like factor 4 (KLF4) were analyzed by real-time PCR. The potential influences of TUG1-proficiency and miR-153-1-deficiency on cell proliferation, migration and viability were determined by colony formation, wound healing and CCK-8 assays, respectively. Cell invasion was evaluated by transwell chamber assay. The regulatory effect of KLF4 on miR-153-1 was interrogated by luciferase reporter assay. Direct association between KLF4 and miR-153-1 promoter was measured by chromatin immunoprecipitation (ChIP) assay. Subcellular localization of TUG1 was determined by fractionization PCR. Enrichment of EZH2 on KLF4 promoter was analyzed by ChIP-PCR. The pro-tumoral activity of TUG1 was determined using xenograft tumor model.
Results: We demonstrated the over-expression of TUG1 and down-regulation of miR-153-1 in CRC. Knockdown of TUG1 or ectopic over-expression of miR-153-1 in SW480 significantly suppressed cell proliferation, migration and viability. TUG1 negatively modulated miR-153-1 expression, and simultaneous expression of TUG1 completely abolished the anti-tumor effect of miR-153-1. We further identified KLF4 as a transcription factor of miR-153-1, which was negatively regulated by TUG1 along with EZH2.
Conclusion: Our study unravels the critical involvement of TUG1/KLF4/miR-153-1 axis in CRC.

Keywords: TUG1, miR-153-1, colorectal cancer, KLF4, EZH2


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