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Long noncoding RNA ADPGK-AS1 promotes cell proliferation, migration, and EMT process through regulating miR-3196/OTX1 axis in breast cancer

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Abstract

Emerging evidences exposed that long noncoding RNAs (lncRNAs) play important roles in various tumor progression including breast cancer (BC). However, the role of lncRNA ADP-dependent glucokinase antisense RNA 1 (ADPGK-AS1) in BC progression remains undiscovered. Hence, this study aimed to investigate the role of ADPGK-AS1 in BC. qRT-PCR was performed to investigate ADPGK-AS1 expression level in BC tissues and cell lines. The effect of ADPGK-AS1 knockdown on BC cellular process was assessed by loss-of-function assay. Luciferase reporter and RIP assay were performed to investigate the combination between ADPGK-AS1 and miR-3196. The combination between miR-3196 and orthodenticle homeobox 1 (OTX1) was verified by luciferase reporter assay. Finally, rescue assays were performed to confirm the effects of ADPGK-AS1/miR-3196/OTX1 axis on BC development. ADPGK-AS1 expression level was upregulated in BC tissues and cell lines. High expression of ADPGK-AS1 predicted poor prognosis for BC patients. Functionally, ADPGK-AS1 promoted cell proliferation, migration, induced epithelial-mesenchymal transition (EMT) process, and suppressed cell apoptosis. Mechanistically, ADPGK-AS1 acted as a miR-3196 sponge to release OTX1 in BC cells. Currently, ADPGK-AS1 acted as a competing endogenous RNA (ceRNA) via modulating miR-3196/OTX1 axis in BC.

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Acknowledgements

The authors thank lab members.

Funding

This study was supported by the Individualized Endocrine Therapy for Luminal Breast Cancer (Fund number: 2015C0003), Effect of Autophagy on Anti-Breast Cancer of 2-Methoxyestradiol and its Mechanism (Fund number: 2018KY729) and Clinical and Curative Effects Prediction of Taxol with or without Carboplatin in the Adjuvant Chemotherapy of Triple-Negative Breast Cancer (Fund number: 2018KY724).

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Authors and Affiliations

  1. Department of Thyroid and Breast, Ningbo Medical Center Lihuili Eastern Hospital/Taipei Medical University Ningbo Medical Center, Ningbo, 315000, Zhejiang Province, China

    Jiahui Yang, Weizhu Wu, Minhua Wu & Jinhua Ding

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  1. Jiahui Yang
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  2. Weizhu Wu
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  3. Minhua Wu
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  4. Jinhua Ding
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Contributions

Jiahui Yang and Weizhu Wu designed the research. Minhua Wu and Jinhua Ding collected materials. Jiahui Yang and Weizhu Wu performed experiments on cells. Minhua Wu and Jinhua Ding recorded the experimental results. All authors contributed to data analysis and article writing.

Corresponding author

Correspondence to Weizhu Wu.

Ethics declarations

This project was approved by the Ethics Committee of the Department of Thyroid and Breast, Ningbo Medical Center Lihuili Eastern Hospital/Taipei Medical University Ningbo Medical Center; all patients had signed the written informed consents before study.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Editor: Tetsuji Okamoto

Jiahui Yang and Weizhu Wu co-first author

Electronic supplementary material

Supplementary Figure 1

A. Overexpression efficiency for ADPGK-AS1 in MDA-MB-453 and MCF-7 cells. B-C. Cell proliferation was measured by cell proliferation assay and colony formation assay after transfection with ADPGK-AS1 expression vector or empty vector. D. Overexpression efficiency for OTX1 in MDA-MB-453 and MCF-7 cells. E-F. The effect of OTX1 overexpression on cell proliferation was detected by cell proliferation assay and colony formation assay. G. Luciferase activity of miR-3196-WT or miR-3196-MUT was measured after transfection with NC or ADPGK-AS1 expression vector. *p < 0.05, **p < 0.01, ***p < 0.001 vs control group. (PNG 441 kb)

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Yang, J., Wu, W., Wu, M. et al. Long noncoding RNA ADPGK-AS1 promotes cell proliferation, migration, and EMT process through regulating miR-3196/OTX1 axis in breast cancer. In Vitro Cell.Dev.Biol.-Animal 55, 522–532 (2019). https://doi.org/10.1007/s11626-019-00372-1

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  • DOI: https://doi.org/10.1007/s11626-019-00372-1

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