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CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA

  • Preclinical study
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Abstract

Background

Triple-negative breast cancer (TNBC) remains a great challenge in clinical treatment due to a shortage of effective therapeutic targets and acquired chemoresistance. Here, we identified the role of an RNA-binding protein, CUG-BP Elav-like family member 6 (CELF6), in the TNBC development and paclitaxel (PTX) chemoresistance.

Methods

Stable CELF6-overexpressing cell lines were established in BT549 and MDA-MB-231 cells. Cell proliferation was determined using cell counting, two-dimensional colony formation, and MTT assay. Meanwhile, cell migration and cell invasion were detected by Transwell assay. Furthermore, the downstream target gene of CELF6 was identified and the direct interaction was further determined by luciferase reporter assay, immunoprecipitation, and RNA pull-down. Additionally, the PTX resistant cell line was established to determine the role of CELF6 in PTX resistance.

Results

CELF6 overexpression suppressed cell proliferation, cell migration, and cell invasion. Mechanistically, Fructose-Bisphosphatase 1 (FBP1) was identified as the target gene of CELF6 and stabilized by CELF6 via binding 3′UTR. CELF6 overexpression mediated inhibition in TNBC development was dependent on FBP1. Moreover, CELF6 overexpression increased the sensitivity to PTX treatment.

Conclusion

CELF6 functions as a tumor suppressor by upregulating FBP 1 expression via stabilizing its mRNA, and thereby inhibits TNBC progression.

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Abbreviations

CELF6:

CUG-BP Elav-like family member 6

TNBC:

Triple-negative breast cancer

PTX:

Paclitaxel

FBP1:

Fructose–bisphosphatase 1

ER:

Estrogen receptors

PR:

Progesterone receptor

HER2:

HUMAN epidermal growth factor receptor 2

RRM:

RNA recognition motifs

IP:

Immunoprecipitation

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Funding

This work was supported by Natural Science Foundation of China (81801952).

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Author notes

  1. Xiaowei Yang and Lu Zhao have contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, Anhui, China

    Xiaowei Yang, Jing Pei, Zhaorui Wang, Jingjie Zhang & Benzhong Wang

  2. Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, Hubei, China

    Lu Zhao

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  1. Xiaowei Yang
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Yang, X., Zhao, L., Pei, J. et al. CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA. Breast Cancer Res Treat 183, 71–82 (2020). https://doi.org/10.1007/s10549-020-05753-9

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