LncRNA DSCAM-AS1 promotes colorectal cancer progression by acting as a molecular sponge of miR-384 to modulate AKT3 expression.

Bo Li,Hai Sun,Jiayu Zhang

doi:10.18632/aging.103243

Abstract

Down Syndrome Cell Adhesion Molecule antisense1 (DSCAM-AS1), a novel long non-coding RNA (lncRNA), reportedly contributes to the development and progression of several cancers. There is a lack of information on its biological role and regulatory mechanism with respect to colorectal cancer (CRC). Here, we discovered that the expression of DSCAM-AS1 exhibited a significant upregulation in CRC tissues and cell lines in comparison with the corresponding control. Increased DSCAM-AS1 expression was associated with poor prognosis for those diagnosed with CRC. Loss-of function assay illustrated that knockdown of DSCAM-AS1 resulted in significant inhibition of cell proliferation, invasion and migration in vitro, and impaired tumor growth in vivo. MicroRNA-384(miR-384) was directly targeted by DSCAM-AS1 in CRC cells, and repression of DSCAM-AS1 inhibited the expression of AKT3, a known target of miR-384 in CRC. In addition, repression of miR-384 or overexpression of AKT3 could partially rescue the inhibitory effect of DSCAM-AS1 knockdown on CRC progression. In summary, DSCAM-AS1 exerted an oncogenic role in CRC by functioning as a competing endogenous RNA of miR-384 to bring about regulation of AKT3 expression. These results implied that DSCAM-AS1 might be a novel therapeutic target for patients suffering from CRC.

Highlights

Colorectal cancer (CRC), a commonly diagnosed digestive malignant tumor, is the third highest reason for tumorassociated mortality around the world [1]
The expression of Down Syndrome Cell Adhesion Molecule (DSCAM)-AS1 in 56 CRC tissues and adjacent normal tissues was detected, and we found a significant increase in its expression in CRC tissues (Figure 1A)
Studies show that DSCAM-AS1 has a role in progression of several cancers, and that it can function as an oncogenic long non-coding RNA (lncRNA) in these cancers [10,11,12,13,14,15,16]

Summary

Introduction

Colorectal cancer (CRC), a commonly diagnosed digestive malignant tumor, is the third highest reason for tumorassociated mortality around the world [1]. Studying the potential mechanisms involved in occurrence and progression of CRC is crucial to explore novel targets for diagnosis and treatment of this disease. Emerging evidence demonstrates that lncRNAs play a crucial regulatory role among various cellular processes, like cell proliferation, invasion, apoptosis and cycle [5, 6]. Studies show that lncRNAs are associated with initiation and development of various cancers [7]. Many lncRNAs are verified to play tumor suppressor or oncogenic role in the progression of CRC [8, 9], suggesting that lncRNAs could serve as a diagnosis marker and therapy agent

Methods

Results

Conclusion