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MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1

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Abstract

Purpose

The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively.

Results

MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3′UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05).

Conclusions

Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments regarding this paper.

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Author notes

    Authors and Affiliations

    1. Department of Emmengey, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China

      D.-Z. Liu & B. Chang

    2. Department of Orthopedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China

      X.-D. Li & Q.-H. Zhang

    3. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, 515041, Guangdong, People’s Republic of China

      Y.-H. Zou

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    1. D.-Z. Liu
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    2. B. Chang
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    Correspondence to Y.-H. Zou.

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    Ethical statement

    The study was approved by the Institutional Review Board of the First Affiliated Hospital of Shantou University Medical College and the methods were carried out in accordance with the approved guidelines. All the patients have been informed and signed informed consent before the experiments.

    Additional information

    D.-Z. Liu and B. Chang contributed equally to this work.

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    Liu, DZ., Chang, B., Li, XD. et al. MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1. Clin Transl Oncol 19, 1133–1140 (2017). https://doi.org/10.1007/s12094-017-1650-1

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    • DOI: https://doi.org/10.1007/s12094-017-1650-1

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