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Cited by 38MicroRNA in disease regulationCancer-related molecular mechanisms researchMechanisms of cancer metastasis

Regulation of the T-box transcription factor Tbx3 by the tumour suppressor microRNA-206 in breast cancer

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Amir, Sumaira, Simion, Catalina, Umeh-Garcia, Maxine, Krig, Sheryl, Moss, Tyler, Carraway, Kermit L, Sweeney, Colleen·2016·British Journal of Cancer
DOI 10.1038/bjc.2016.73PMC PMC4865973
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Abstract

BACKGROUND: The Tbx3 transcription factor is over-expressed in breast cancer, where it has been implicated in proliferation, migration and regulation of the cancer stem cell population. The mechanisms that regulate Tbx3 expression in cancer have not been fully explored. In this study, we demonstrate that Tbx3 is repressed by the tumour suppressor miR-206 in breast cancer cells. METHODS: Bioinformatics prediction programmes and luciferase reporter assays were used to demonstrate that miR-206 negatively regulates Tbx3. We examined the impact of miR-206 on Tbx3 expression in breast cancer cells using miR-206 mimic and inhibitor. Gene/protein expression was examined by quantitative reverse-transcription-PCR and immunoblotting. The effects of miR-206 and Tbx3 on apoptosis, proliferation, invasion and cancer stem cell population was investigated by cell-death detection, colony formation, 3D-Matrigel and tumorsphere assays. RESULTS: In this study, we examined the regulation of Tbx3 by miR-206. We demonstrate that Tbx3 is directly repressed by miR-206, and that this repression of Tbx3 is necessary for miR-206 to inhibit breast tumour cell proliferation and invasion, and decrease the cancer stem cell population. Moreover, Tbx3 and miR-206 expression are inversely correlated in human breast cancer. Kaplan-Meier analysis indicates that patients exhibiting a combination of high Tbx3 and low miR-206 expression have a lower probability of survival when compared with patients with low Tbx3 and high miR-206 expression. These studies uncover a novel mechanism of Tbx3 regulation and identify a new target of the tumour suppressor miR-206. CONCLUSIONS: The present study identified Tbx3 as a novel target of tumour suppressor miR-206 and characterised the miR-206/Tbx3 signalling pathway, which is involved in proliferation, invasion and maintenance of the cancer stem cell population in breast cancer cells. Our results suggest that restoration of miR-206 in Tbx3-positive breast cancer could be exploited for therapeutic benefit.

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Authors
Amir, S., Simion, C., Umeh-Garcia, M., Krig, S., Moss, T., Carraway, K. L., & Sweeney, C.
Affiliations
  • University of California, Davis (US)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Sweeney, Colleen
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2016-04-21
Volume
114
Issue
10
Pages
1125-1134
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/bjc.2016.73
PMC
PMC4865973
OpenAlex
W2338653279
Cited by
38
References
64
Citations by year
2025: 3 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 3
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Cancer (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Cancer Research Coordinating Committee
  • National Cancer Institute (R01CA166412)
  • National Institute of General Medical Sciences (T32GM007377)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords
TBX3, miR-206, breast cancer, microRNA regulation, transcription factor repression, tumor suppressor microRNA, cancer stem cells, cell proliferation, cell invasion, apoptosis, patient survival, therapeutic target
MeSH terms
Breast Neoplasms, Cell Movement, Female, Humans, Prognosis, Gene Expression Regulation, Neoplastic, Survival Analysis, Apoptosis, Computational Biology, T-Box Domain Proteins, MicroRNAs, Cell Line, Tumor, Cell Proliferation, MCF-7 Cells

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