Back to Journals » Cancer Management and Research » Volume 11

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


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Harikrishna 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

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]