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In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/β-catenin signaling pathway

Ling-Yu Kong, Mei Xue _, Qing-Cai Zhang and Chuan-Fu Su

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Oncotarget. 2017; 8:15507-15519. https://doi.org/10.18632/oncotarget.14662

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Abstract

Ling-Yu Kong1, Mei Xue2, Qing-Cai Zhang3, Chuan-Fu Su1

1Department of Breast, Linyi Cancer Hospital, Linyi 276000, P.R. China

2Department of Pathology, Linyi Cancer Hospital, Linyi 276000, P.R. China

3Operating Theatre, Daqing Oilfield General Hospital, Daqing 163000, P.R. China

Correspondence to:

Mei Xue, email: [email protected]

Keywords: microRNA-27a, secreted frizzled-related protein 1, Wnt/β-catenin signaling pathway, breast cancer, proliferation

Received: June 21, 2016     Accepted: December 12, 2016     Published: January 14, 2017

ABSTRACT

This study aims to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/β-catenin signaling pathway. BC and normal breast tissues were obtained from 396 female BC patients and 308 female patients with benign breast lesions respectively. Human normal mammary epithelial (MCF-10A) and BC cell lines (BT-20, MCF-7, T-47D and MDA-MB-231) were cultured. After cell transfection, BC cells were assigned to six groups: control, miR-27a mimics, miR-27a inhibitors, negative control (NC), si-SFRP1 and si-SFRP1 + miR-27a inhibitors groups. qRT-PCR assay and Western blot were employed to detect the expressions of miR-27a, SFRP1, Wnt, β-catenin and GSK3β. MTT assay, wound-healing test and Transwell assay were used to test cell proliferation, migration and invasion. BC tissues were found to have higher miR-27a expression and lower SFRP1 mRNA and protein expressions than MCF-10A cells and normal breast tissues. Compared with the control and NC groups, the miR-27a mimics and si-SFRP1 groups exhibited down-regulation of SFRP1, up-regulation of Wnt, β-catenin and GSK3β, and promotion of cell proliferation, migration and invasion. The miR-27a inhibitor group showed up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the miR-27a mimic group. The si-SFRP1 + miR-27a inhibitors group also exhibited up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the si-SFRP1 group. miR-27a may activate the Wnt/β-catenin signaling pathway by negatively regulating SFRP1 to promote the proliferation, migration and invasion of BC cells.


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