lnc‑MICAL2‑1 sponges miR‑25 to regulate DKK3 expression and inhibits activation of the Wnt/β‑catenin signaling pathway in breast cancer

Yao,Jia; Li,Guanqiao; Liu,Minfeng; Yang,Shiping; Su,Huiluan; Ye,Changsheng

doi:10.3892/ijmm.2021.5078

lnc‑MICAL2‑1 sponges miR‑25 to regulate DKK3 expression and inhibits activation of the Wnt/β‑catenin signaling pathway in breast cancer

Authors:
- Jia Yao
- Guanqiao Li
- Minfeng Liu
- Shiping Yang
- Huiluan Su
- Changsheng Ye
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Affiliations: The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510650, P.R. China, Department of General Surgery‑Breast Center, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510650, P.R. China, Department of Radiotherapy, Hainan General Hospital, Haikou, Hainan 570311, P.R. China
Published online on: December 30, 2021 https://doi.org/10.3892/ijmm.2021.5078
Article Number: 23

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Abstract

The Dickkopf 3 (DKK3) protein antagonizes the Wnt receptor complex in the Wnt signaling pathway; however, to date, there have been no relevant studies investigating its upstream regulatory mechanism in breast cancer (BC), to the best of our knowledge. The present study aimed to explore whether long non‑coding RNA MICAL2‑1 (lnc‑MICAL2‑1) sponged microRNA (miR)‑25 to regulate DKK3 and inhibit activation of the Wnt/β‑catenin signaling pathway. The Atlas of non‑coding RNA in Cancer database was used to measure the expression levels of lnc‑MICAL2‑1 and their correlation with DKK3 expression levels. In addition, cell proliferation, invasion and migration were determined following the silencing or overexpression of lnc‑MICAL2‑1. The binding between lnc‑MICAL2‑1 and miR‑25, or miR‑25 and DKK3 was verified using RNA pull‑down and dual‑luciferase reporter assays. The effects of overexpression or knockdown of lnc‑MICAL2‑1 on DKK3 expression and the Wnt signaling pathway were further evaluated in a nude mouse xenograft model. The results revealed that, compared with in adjacent normal tissue, the expression levels of lnc‑MICAL2‑1 were downregulated in BC tissues, and the expression levels of lnc‑MICAL2‑1 were found to be positively correlated with DKK3 expression. The overexpression of lnc‑MICAL2‑1 in BC cells upregulated the mRNA expression levels of DKK3 and inhibited their proliferation. Results from the RNA pull‑down and dual luciferase reporter assays validated that lnc‑MICAL2‑1 could bind to miR‑25, which targets DKK3. The in vivo experimental data demonstrated that lnc‑MICAL2‑1 inhibited tumor growth via regulating the Wnt signaling pathway. In conclusion, the findings of the present study highlighted a novel molecular mechanism through which lnc‑MICAL2‑1 may regulate the DKK3‑mediated Wnt signaling pathway in BC, highlighting potential targets for the treatment of the disease.

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