Research Paper Volume 12, Issue 12 pp 11653—11666
Long non-coding RNA RP11-59H7.3 promotes cell proliferation and invasion metastasis in colorectal cancer by miR-139-5p/NOTCH1 axis
- 1 Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- 2 Jiangxi Medical College of Nanchang University, Nanchang, China
- 3 Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
Received: January 16, 2020 Accepted: May 17, 2020 Published: June 6, 2020
https://doi.org/10.18632/aging.103331How to Cite
Copyright © 2020 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Increasing evidence suggests long non-coding RNAs (lncRNAs) are distinctively expressed in several cancers. However, the functions of these lncRNAs in cancer development remain unknown. In the current study, we report high expression of a novel lncRNA, RP11-59H7.3, and its association with prognosis in colorectal cancer (CRC) patients. Functional analyses of this lncRNA revealed its role in promoting proliferation and progression of the cell cycle, as well as enhancement of cell migration and invasion. Furthermore, our results revealed that knockdown of RP11-59H7.3 promoted cell apoptosis, with luciferase reporter assays showing that it directly binds to miR-139-5p. Knockdown of this lncRNA significantly reduced expression of NOTCH1, a direct target of miR-139-5p. Additionally, we show that suppression NOTCH1 by miR-139-5p could be partially rescued by overexpressing RP11-59H7.3. Analysis of the relationship between RP11-59H7.3 and miR-139-5p, in CRC tissues, showed a negative correlation while a positive association was observed between the RP11-59H7.3 expression and levels of NOTCH1. Taken together, these results demonstrated that the RP11-59H7.3/miR-139-5p/NOTCH1 axis functions as a key regulator in CRC metastasis. RP11-59H7.3 represents a potential biomarker for CRC diagnosis and could be an important target for development of novel therapies to manage the disease.