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Long Non-Coding RNA LOXL1-AS1 Enhances Colorectal Cancer Proliferation, Migration and Invasion Through miR-708-5p/CD44-EGFR Axis

Authors Wu X, Cui F, Chen Y, Zhu Y, Liu F

Received 23 April 2020

Accepted for publication 13 July 2020

Published 3 August 2020 Volume 2020:13 Pages 7615—7627

DOI https://doi.org/10.2147/OTT.S258935

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Takuya Aoki


Xiaoyu Wu,1 Facai Cui,1 Yu Chen,2 Ya Zhu,1 Fengzhen Liu1

1Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China

Correspondence: Xiaoyu Wu Email xiaoyuwhn@163.com

Introduction: Colorectal cancer (CRC), the third most common cancer worldwide, involves a physiological and pathological long non-coding RNA (lncRNA) paradigm shift. It has been reported that the lncRNA LOXL1-AS1 affects tumor development for many kinds of cancers, but its functions and mechanisms in CRC remain unknown.
Methods: Expression levels of LOXL1-AS1 and miR-708-5p within CRC tissues and cell lines were measured using qRT-PCR. The performance of gain-of-function and loss-of-function assays was aimed at examining the effects of LOXL1-AS1 and miR-708-5p; colony formation and cell viability assays were carried out to measure cell multiplication; and Transwell migration and wound-healing assays were carried out for the measurement of cell migration and invasion. Luciferase reporter assay was used to verify the interactions between LOXL1-AS1 and miR-708-5p and between miR-708-5p and the CD44-EGFR signaling pathway. Finally, expression of CD44 and EGFR proteins was measured by Western blot and immunofluorescence assays.
Results: In this study, we reveal that the regulation of lncRNA LOXL1-AS1 occurs within CRC based on the correlation with poor clinical outcomes. LOXL1-AS1 knockdown along with miR-708-5p overpresentation in CRC cell lines inhibited cell multiplication, migration, and invasion. The inhibiting effect of LOXL1-AS1 knockdown on CRC was reversed by upregulating the CD44-EGFR signal pathway. From the perspective of mechanism, LOXL1-AS1 imposes sponging upon miR-708-5p and thereby promotes the CD44-EGFR signal pathway in CRC cells.
Discussion: This study demonstrated that lncRNA LOXL1-AS1 enhances multiplication, migration, invasion, and progression of CRC by sponging miR-708-5p to regulate the CD44-EGFR signal pathway.

Keywords: colorectal cancer, LOXL1-AS1, CD44-EGFR signal pathway, miR-708-5p, migration

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