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LncRNA HOTAIR as a ceRNA is related to breast cancer risk and prognosis

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Abstract

Purpose

Breast cancer (BC) is one of the biggest threats to women’s health. LncRNA HOTAIR is related to the recurrence and metastasis of BC. Whether HOTAIR can serve as an effective biomarker to distinguish BC patients with different prognosis need to be further studied.

Methods

The miRNA and mRNA expression profile data of BC patients were downloaded from TCGA database. Univariate Cox regression was used to screen differential expression genes (DEGs). The miRcode database and miRWalk database were used to predict miRNA binding to HOTAIR and binding sites of miRNAs, respectively. Kaplan-Meier (KM) analysis was used to estimate the overall survival rate of BC patients. Finally, qRT-PCR and western blot were applied to evaluate the expression level of HOTAIR and mRNAs between BC cells and normal mammary cells.

Results

The patients with high HOTAIR expression had poor prognosis in BC. Totally 10 genes correlated with BC prognosis were identified from 170 DEGs, among which PAX7, IYD, ZIC2, MS4A1, TPRXL, CD24, LHX1 were positively correlated with HOTAIR, while CHAD, NPY1R, TPRG1 were opposite. The levels of IYD, ZIC2, CD24 mRNA and protein were increased in BC tissues and BC cells. In BC cells, the levels of IYD, ZIC2 and CD24 mRNA and protein were significantly increased in HOTAIR overexpressed group. HOTAIR had the strongest interaction with hsa-miR-129-5p, followed by hsa-miR-107.

Conclusion

HOTAIR regulated the expression of downstream genes by interacting with 8 miRNAs and ultimately affected the prognosis of BC patients.

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Data availability

The data that support the findings of this study are openly available in the Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/tcga/).

Abbreviations

BC:

Breast cancer

lncRNAs:

Long noncoding RNAs

ceRNA:

Competitive endogenous RNA

HOTAIR:

HOX transcript antisense RNA

miRNAs:

MicroRNAs

HR:

Hazard ratio

LIHC:

Liver hepatocellular carcinoma

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Acknowledgements

Not applicable.

Funding

This work was supported by the Projects of Bengbu Medical College Natural Science Foundation (grand number 2020byzd061).

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Author notes

    Authors and Affiliations

    1. Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

      Liyu Qian

    2. Department of Breast and Thyroid Surgery, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China

      Li Li

    3. Department of Cardiac Surgery, Xuanwu Hospital of Capital Medical University, Beijing, China

      Yang Li

    4. Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China

      Shen Li

    5. Department of Immunology, College of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China

      Bo Zhang

    6. Department of Clinical Laboratory, Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin, 300170, China

      Yu Zhu

    7. Department of Cell Biology, College of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China

      Bing Yang

    8. Department of Clinical Laboratory, Tianjin Third Center Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China

      Yu Zhu

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    Contributions

    Liyu Qian and Li Li contributed to the study conception and design. Material preparation, data curation, analysis and validation were performed by Liyu Qian, Li Li and Shen Li. The first draft of the manuscript was written by all authors. Yu Zhu and Bing Yang edited and reviewed the manuscript. All authors read and approved the final manuscript. Yang Li and Bo Zhang made great contribution during the revision process.

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    Correspondence to Bo Zhang, Yu Zhu or Bing Yang.

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    Ethics approval and consent to participate

    All experiments were approved by the medical ethics committee of the First Affiliated Hospital of Bengbu Medical College, conformed to the declaration of Helsinki, and informed consent was obtained from all subjects.

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    The authors declare that they have no conflicts of interest.

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    Liyu Qian and Li Li contributed equally to this work.

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    Qian, L., Li, L., Li, Y. et al. LncRNA HOTAIR as a ceRNA is related to breast cancer risk and prognosis. Breast Cancer Res Treat 200, 375–390 (2023). https://doi.org/10.1007/s10549-023-06982-4

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    • DOI: https://doi.org/10.1007/s10549-023-06982-4

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