Related Experiment Video
Updated: Dec 17, 2025
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA
Xiaowei Yang1, Lu Zhao2, Jing Pei3
1Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, Anhui, China. yangxiaowei@ahmu.edu.cn.
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.
Insights
CUG-BP Elav-like family member 6 (CELF6) acts as a tumor suppressor in triple-negative breast cancer (TNBC). Overexpressing CELF6 inhibits TNBC progression and enhances sensitivity to paclitaxel (PTX) chemotherapy.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Triple-negative breast cancer (TNBC) presents significant clinical challenges due to limited therapeutic targets and acquired chemoresistance.
- Identifying novel therapeutic targets is crucial for improving TNBC treatment outcomes.
Purpose of the Study:
- To investigate the role of the RNA-binding protein CUG-BP Elav-like family member 6 (CELF6) in TNBC development.
- To determine the involvement of CELF6 in paclitaxel (PTX) chemoresistance in TNBC.
Main Methods:
- Establishment of CELF6-overexpressing cell lines (BT549, MDA-MB-231).
- Assessment of cell proliferation, migration, and invasion using standard assays.
- Identification and validation of CELF6 downstream targets (Fructose-Bisphosphatase 1 - FBP1) through luciferase reporter, immunoprecipitation, and RNA pull-down assays.
- Evaluation of CELF6's role in PTX resistance using a resistant cell line model.
Main Results:
- CELF6 overexpression significantly suppressed TNBC cell proliferation, migration, and invasion.
- Fructose-Bisphosphatase 1 (FBP1) was identified as a direct target gene of CELF6, with CELF6 stabilizing FBP1 mRNA via 3'UTR binding.
- The tumor-suppressive effects of CELF6 in TNBC were dependent on FBP1.
- CELF6 overexpression enhanced TNBC cell sensitivity to paclitaxel (PTX) treatment.
Conclusions:
- CELF6 functions as a tumor suppressor in TNBC by upregulating FBP1 expression through mRNA stabilization.
- CELF6 inhibits TNBC progression and may serve as a potential therapeutic target to overcome chemoresistance.
