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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Opinion Article

ORLNC1 Suppresses Cell Growth in HER2-Positive Breast Cancer via miRNA-296 Sponging

Author(s): Xueyuan Cheng, Zhong Huang, Anchao Pan and Di Long*

Volume 23, Issue 4, 2023

Published on: 20 August, 2022

Page: [289 - 299] Pages: 11

DOI: 10.2174/1566524022666220603113550

Price: $65

Abstract

Background: Accumulating research has demonstrated that aberrant levels of long noncoding RNAs (LncRNAs) are related to cancer progression. The effects of ORLNC1 in HER2+ breast cancer have yet to be explored.

Methods: Real-time PCR was used to examine the expression of LncRNA ORLNC1 in HER+ breast cancer. CCK-8, wound healing and cell invasion assays were used to examine the effect of LncRNA ORLNC1 on HER+ breast cancer cells. Luciferase reporter assay was utilized to determine the regulatory relationship between LncRNA ORLNC1 and miR-296. Western blotting was used to measure the expression of PTEN. Xenograft mouse model was used to examine the effect of LncRNA ORLNC1 on tumor progression in vivo.

Results: In this study, our findings revealed downregulation of ORLNC1 in HER2+ breast cancer specimens and cell lines. Low levels of ORLNC1 were related to poor prognosis and advanced cancer stage. Using gain- and loss-of-function assays, the ability of these tumor cells to proliferate was found to be inhibited by ORLNC1 in vitro and in vivo. Further analyses revealed that miR-296/PTEN axis is directly targeted by ORLNC1. Consequently, over-expression of miR-296 efficiently abrogated the upregulation of PTEN induced by ORLNC1, suggesting that ORLNC1 positively regulates PTEN expression by competitively binding to miR-296.

Conclusion: Our results indicate that lncRNA ORLNC1 acts as a tumor suppressor by regulating the miR-296/PTEN axis in HER2+ breast cancer.

Keywords: lncRNAs, ORLNC1, miR-296, PTEN, HER2+ breast cancer, RNAs

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