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Updated: Feb 8, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction
Background/Aims:
Triple negative breast cancer (TNBC) is resistant to conventional chemotherapy due to high proportions of cancer stem cells (CSCs). The aim of this study is to unravel the miR-137-mediated regulatory mechanism of B-cell lymphoma/leukemia 11A (BCL11A) in TNBC.
Methods:
A corhort of 34 TNBC tumor tissues and paired adjacent normal tissues, as well as 25 non-TNBC tumor tissues and paired adjacent normal tissues were collected post-operatively from patients with breast cancer. Q-PCR was performed to determine the mRNA levels of miR-137 and BCL11A in breast tissues and cell lines. Bioinformatics analysis and dual luciferase reporter assay were used to verify the direct interaction between miR-137 and BCL11A. After up-/down-regulation of BCL11A, miR-137, or DNMT1 via lentiviral transduction in TNBC cell lines SUM149 and MDA-MB-231 cells, Q-PCR and Western blot assays were used to detect the expression levels of BCL11A, DNA methyltransferases 1 (DNMT1), and Islet-1 (ISL1). Mammosphere assay was conducted to assess tumorosphere formation ability of cells, coupled with flow cytometry to determine the percentage of breast cancer stem cells. Co-immunoprecipitation assay was used to determine the interaction between BCL11A and DNMT1. Xenograft tumorigenesis assay was performed to monitor tumor formation in vivo.
Results:
BCL11A was highly expressed in TNBC, whereas miR-137 was significantly lower in both TNBC tissues and cell lines. miR-137 suppressed BCL11A expression at both mRNA and protein levels by directly targeting its 3'UTR. In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of BCL11A reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. Furthermore, BCL11A interacted with DNMT1 in TNBC cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing ISL1 expression both in vitro, and in vivo.
Conclusions:
By perturbing BCL11A-DNMT1 interaction, miR-137 impairs cancer stemness and suppresses tumor development in TNBC.
Insights
MicroRNA-137 (miR-137) targets B-cell lymphoma/leukemia 11A (BCL11A) in triple-negative breast cancer (TNBC). This interaction impairs cancer stemness and suppresses tumor development by affecting the BCL11A-DNMT1 axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) exhibits resistance to chemotherapy, attributed to a high proportion of cancer stem cells (CSCs).
- Understanding the molecular mechanisms regulating CSCs in TNBC is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the regulatory role of microRNA-137 (miR-137) in triple-negative breast cancer (TNBC).
- To elucidate the mechanism by which miR-137 targets B-cell lymphoma/leukemia 11A (BCL11A) and influences cancer stemness and tumor development.
Main Methods:
- Analysis of miR-137 and BCL11A expression in TNBC and non-TNBC tissues and cell lines.
- Bioinformatics and dual luciferase reporter assays to confirm direct interaction between miR-137 and BCL11A.
- In vitro (mammosphere assays, flow cytometry) and in vivo (xenograft tumorigenesis) studies to assess the impact of miR-137 and BCL11A on cancer stemness and tumor growth.
Main Results:
- BCL11A expression was elevated, while miR-137 levels were reduced in TNBC.
- miR-137 directly targets BCL11A, suppressing its expression and consequently reducing cancer stem cell populations and tumor formation.
- BCL11A interacts with DNMT1, and their combined silencing inhibits TNBC stemness and tumorigenesis via ISL1 suppression.
Conclusions:
- miR-137 plays a critical role in suppressing TNBC progression by targeting BCL11A.
- Perturbing the BCL11A-DNMT1 interaction through miR-137 intervention offers a potential therapeutic strategy for TNBC by targeting cancer stemness.
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