Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2019; 25(14): 1697-1714
Published online Apr 14, 2019. doi: 10.3748/wjg.v25.i14.1697
Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro
Xiao-Dong Wang, Jian Lu, Yun-Shou Lin, Chao Gao, Feng Qi
Xiao-Dong Wang, Jian Lu, Yun-Shou Lin, Chao Gao, Feng Qi, Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
Author contributions: Qi F designed and coordinated the research; Wang XD performed the majority of experiments, analyzed the data, and wrote the paper; Lu J, Lin YS, and Gao C contributed new reagents or analytic tools.
Supported by the National Natural Science Foundation of China, No. 81570375.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethical No. IRB2015-YX-018) and was conducted in strict compliance with the Declaration of Helsinki.
Conflict-of-interest statement: The authors report no conflicts of interest in this work.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Feng Qi, FRCS (Gen Surg), MD, PhD, Academic Research, Chief Doctor, Director, Doctor, Full Professor, Professor, Research Scientist, Senior Researcher, Senior Scientist, Surgeon, Surgical Oncologist, Teacher, Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China. qf@medmail.com.cn
Telephone: +86-13752115987 Fax: +86-22-60363901
Received: January 13, 2019
Peer-review started: January 14, 2019
First decision: February 21, 2019
Revised: March 6, 2019
Accepted: March 15, 2019
Article in press: March 16, 2019
Published online: April 14, 2019
Processing time: 91 Days and 1 Hours
Abstract
BACKGROUND

Long non-coding RNAs (lncRNAs) are widely involved in tumor regulation. Nevertheless, the role of the lncRNA cancer susceptibility 19 (CASC19) in colorectal cancer (CRC) has yet to be fully clarified.

AIM

To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.

METHODS

CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR (qRT-PCR). CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay. In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.

RESULTS

CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines (P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC (P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion, migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1 (CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5p reversed the effect of CASC19 on cell proliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.

CONCLUSION

CASC19 positively regulates CEMIP expression through targeting miR-140-5p. CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.

Keywords: Colorectal cancer; Long non-coding RNA; MicroRNA; Proliferation; Metastasis

Core tip: The long non-coding RNA cancer susceptibility 19 is highly expressed in colorectal cancer tissues. In vitro studies have shown that the long non-coding RNA cancer susceptibility 19 may regulate the proliferation, epithelial-mesenchymal transition, and metastasizing ability of colorectal cancer cells by regulating microRNA-140-5p, as well as cell migration by inducing hyaluronidase 1.