A Long Non-coding RNA LINC00461-dependent Mechanism Underlying Breast Cancer Invasion and Migration Via the MiR-144-3p/KPNA2 Axis

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2020 May 2

PMID 32355466

Citations 11

Authors

Qiang Zhang

Xiaoyan Jin

Wenbiao Shi

Xin Chen

Wenyang Pang

Xiaodong Yu

Linjun Yang

Affiliations

Soon will be listed here.

Abstract

Background: The purpose of this study was to explore the regulatory mechanism of the long non-coding RNA (lncRNA) LINC00461 underlying the breast cancer invasion and migration via the miR-144-3p/KPNA2 axis.

Methods: Bioinformatics methods were applied to screen differentially expressed mRNAs, miRNAs and lncRNAs for construction of a competing endogenous RNA (ceRNA) network. LINC00461, KPNA2 and miR-144-3p were identified, and KPNA2 was predicted to be a target of miR-144-3p and significantly correlated with breast cancer prognosis. To make the findings more convincible, we used qRT-PCR to detect the expression levels of LINC00461 and miR-144-3p in breast cancer cells, and conducted western blot to determine KPNA2 protein level. Then, RIP was performed to assess the combination between miR-144-3p and LINC00461 or KPNA2, and dual-luciferase reporter assay was used to validate the targeted relationship between miR-144-3p and KPNA2. Furthermore, Transwell was employed for the examination of cell invasion and migration in breast cancer.

Results: LINC00461 was predicted to regulate KPNA2 through sponging miR-144-3p as revealed by the ceRNA network. Besides, LINC00461 and KPNA2 were found to be remarkably highly-expressed in breast cancer cells, while miR-144-3p was poorly-expressed. Silencing LINC00461 could promote miR-144-3p expression, thus inhibiting cell invasion and migration. In addition, KPNA2 was confirmed to be a direct target of miR-144-3p. Silencing miR-144-3p or overexpressing KPNA2 could reverse the inhibitory effect of LINC00461 silencing on cell invasion and migration in breast cancer.

Conclusion: LINC00461 promoted the expression of KPNA2 by competitively binding to miR-144-3p, thereby promoting the invasion and migration of breast cancer cells.

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