Long non-coding RNA RP11-59H7.3 promotes cell proliferation and invasion metastasis in colorectal cancer by miR-139-5p/NOTCH1 axis.

Xiaojian Zhu,Zhengming Zhu,Kang Lin,Chen Luo,Fanqin Bu

doi:10.18632/aging.103331

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.

Highlights

Colorectal cancer (CRC) is one of the most common malignancies, accounting for an estimated 1.1 (6.1%) million new cancer cases and 0.88 (9.2%) million cancer-related deaths per year worldwide [1]
Our results revealed a unique pathway for RP11-59H7.3/ NOTCH1/miR-139-5p regulation in colorectal cancer, suggesting that RP11-59H7.3 is a new biomarker for prognosis
To investigate expression profiles of RP11-59H7.3 in colorectal cancer (CRC), we first measured the mRNA levels of the long non-coding RNAs (lncRNAs) in 68 pairs of CRC and paired adjacent healthy tissues using RT-qPCR

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignancies, accounting for an estimated 1.1 (6.1%) million new cancer cases and 0.88 (9.2%) million cancer-related deaths per year worldwide [1]. NEAT1 stimulates signaling of Wnt/βcatenin and enhances CRC progression through a synergistic interaction with DDX5 [12, 13]. These findings indicate that several lncRNAs are individually expressed in CRC, participate in initiation and progression of CRC by competitively binding onto miRNAs and influence expression of several target molecules. It is, critical to unravel the specific lncRNAs associated with CRC to improve personalized therapy for patients

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Results

Conclusion