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Long non-coding RNA A1BG-AS1 promotes tumorigenesis in breast cancer by sponging microRNA-485-5p and consequently increasing expression of FLOT1 expression

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Abstract

The dysregulated long non-coding RNA A1BG antisense RNA 1 (A1BG-AS1) has been implicated in the oncogenicity of hepatocellular carcinoma. Using reverse transcription quantitative polymerase chain reaction in this study, we detected A1BG-AS1 expression in breast cancer and elucidated the regulatory functions and exact mechanisms of A1BG-AS1 in breast cancer cells. The regulatory functions of A1BG-AS1 were examined in vitro using the Cell Counting Kit-8 assay, flow cytometric, and Transwell migration and invasion assays and in vivo through tumor xenograft experiments. In addition, we performed bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and rescue experiments to verify the interaction among A1BG-AS1, microRNA-485-5p (miR-485-5p), and flotillin-1 (FLOT1) in breast cancer. We found A1BG-AS1 to be highly expressed in breast cancer tissues and cell lines. In terms of function, depleted A1BG-AS1 markedly suppressed cell proliferation, accelerated cell apoptosis, and hindered cell migration and invasion in breast cancer. Furthermore, A1BG-AS1 interference reduced tumor growth in vivo. Mechanistic investigations confirmed that A1BG-AS1 directly interacted with miR-485-5p as a molecular sponge. We demonstrated that FLOT1 is a direct target of miR-485-5p, which could be positively regulated by A1BG-AS1 by competing for miR-485-5p. Rescue experiments clearly showed that the downregulation of miR-485-5p and upregulation of FLOT1 were capable of reversing the anticancer activities of A1BG-AS1 deficiency in terms of breast cancer cell malignancy. A1BG-AS1 acts as a miR-485-5p sponge and subsequently increases FLOT1 expression in breast cancer cells, ultimately facilitating cancer progression. Hence, the A1BG-AS1/miR-485-5p/FLOT1 pathway might offer a novel therapeutic perspective for breast cancer.

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Funding

This study was supported by the Lishui key medical discipline construction project (2017ZDXK10) and the Lishui Science and Technology Project (2019SJZC40).

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Authors and Affiliations

  1. Department of Breast Surgery, Lishui Hospital, Zhejiang University School of Medicine, 289 Kuocang Road, Lishui, 323000, Zhejiang, China

    Shibin Cai, Yi Zhou, Ying Pan, Pengpeng Liu, Kaijie Yu & Shuzheng Chen

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  1. Shibin Cai
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  2. Yi Zhou
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  3. Ying Pan
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  4. Pengpeng Liu
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  5. Kaijie Yu
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Correspondence to Shuzheng Chen.

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The authors declare that they have no competing interests.

Ethical approval

The Ethics Committee of the Lishui Hospital approved the use of human tissue samples (approval number: ECLSH-2019-168), and the experimental steps were conducted in accordance with the Declaration of Helsinki. The Institutional Animal Care and Use Committee of Lishui Hospital approved all animal care, use, and euthanasia.

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Cai, S., Zhou, Y., Pan, Y. et al. Long non-coding RNA A1BG-AS1 promotes tumorigenesis in breast cancer by sponging microRNA-485-5p and consequently increasing expression of FLOT1 expression. Human Cell 34, 1517–1531 (2021). https://doi.org/10.1007/s13577-021-00554-8

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  • DOI: https://doi.org/10.1007/s13577-021-00554-8

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