MicroRNA profiling identifies Forkhead box transcription factor M1 (FOXM1) regulated miR-186 and miR-200b alterations in triple negative breast cancer

Hamurcu, Zühal; Şener, Elif Funda; Taheri, Serpil; Nalbantoğlu, Ufuk; Kökçü, Nesrin Delibaşı; Tahtasakal, Reyhan; Çınar, Venhar; Güler, Ahsen; Özkul, Yusuf; Dönmez-Altuntaş, Hamiyet; Ozpolat, Bulent

doi:10.1016/j.cellsig.2021.109979

Cited by 18 publications

(19 citation statements)

References 78 publications

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“…Additional miRNAs established to target FOXM1 in ovarian cancer are miR-134 [ 195 , 196 , 197 , 198 , 199 ] and miR-216b [ 200 , 201 , 202 , 203 ]. Interestingly, a recent report indicates that FOXM1 acts as a transcriptional regulator of several miRNA molecules in triple-negative breast cancer, which has a similar molecular profile to HGSC [ 204 ]. Taken together, these data indicate that ncRNA alterations play a key role in promoting FOXM1 expression in cancer, including ovarian cancer, and that FOXM1 itself can function in miRNA dysregulation.…”

Section: Foxm1 Is Overexpressed and Activated In Ovarian Cancermentioning

confidence: 99%

FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

Liu

Barger

Karpf

2021

Cancers

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Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. In this review article, we address the current knowledge regarding the mechanisms of regulation and oncogenic functions of FOXM1, particularly in the context of ovarian cancer. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell (CSC) properties, (5) genomic instability, and (6) altered cellular metabolism. We additionally discuss the evidence for FOXM1 as a cancer biomarker, describe the rationale for FOXM1 as a cancer therapeutic target, and provide an overview of therapeutic strategies used to target FOXM1 for cancer treatment.

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Section: Foxm1 Is Overexpressed and Activated In Ovarian Cancermentioning

confidence: 99%

FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

Liu

Barger

Karpf

2021

Cancers

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“…We and others have previously shown that FOXM1 is upregulated in TNBC cells and required for cell proliferation and survival in TNBC [21,27]. Also, according to analysis of The Cancer Genome Atlas breast cancer data base, we have reported that FOXM1 expression is associated with poor prognosis and shorter patient survival in breast cancer [25]. Therefore, we hypothessized that 5-HT/ 5-HT7 receptor signaling may induce FOXM1 to promote cell proliferation in TNBC cells.…”

Section: -Ht Modulates 5-ht7 and Foxm1 Signaling In Tnbc Cellsmentioning

confidence: 83%

“…MCF10A cells were cultured in DMEM/F12 supplemented with 5% horse serum, epidermal growth factor, hydrocortisone, insulin, and cholera toxin (Calbiochem). Cells were cultured at 37°C in a humidi ed incubator with 5% CO 2 [21,24,25]. 5-HT (H9523) and Metergoline (M3668) were purchased from Sigma-Aldrich (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

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Serotonin 5-HT7 Receptor Is A Biomarker Poor Prognostic Factor And Induces Proliferation of Triple Negative Breast Cancer Cells Through FOXM1

Çınar

Hamurcu

Güler

et al. 2022

Preprint

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Purpose: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with poor prognosis and shorter survival due to significant genetic heterogeneity, drug resistance and lack of effective targeted therapeutics. Therefore, novel molecular targets and therapeutic strategies are needed to improve patient survival. Serotonin (5-hydroxytriptamine, 5-HT) has been shown to induce growth stimulatory effects in breast cancer. However, the molecular mechanisms by which 5-HT exerts its oncogenic effects in TNBC still are not well understood. Methods: Normal breast epithelium (MCF10A) and two TNBC cells (MDA-MB-231, BT-546) and MCF-7 cells (ER+) were used to investigate effects of 5-HT7 receptor. Small interfering RNA (siRNA)-based knockdown and metergoline (5-HT7 antagonist) were used to inhibit the activity of 5-HT7. Cell proliferation and colony formation were evaluated using MTS cell viability and colony formation assays, respectively. Western blotting was used to investigate 5-HT7, FOXM1 and its downstream targets protein expressions.Results: We demonstrated that 5-HT induces cell proliferation of TNBC cells and expression of 5-HT7 receptor and FOXM1 oncogenic transcription factor. We found that expression of 5-HT7 receptor is upregulated in TNBC cells and higher 5-HT7 expression is associated with poor patient prognosis and shorter patient survival. Genetic and pharmacological inhibition of 5-HT7 by siRNA and metergoline, respectively, suppressed TNBC cell proliferation and FOXM1 and its downstream mediators, including eEF2-Kinase (eEF2K) and cyclin-D1. Conclusion: Our findings suggest for the first time that the 5-HT7 receptor promotes FOXM1, eEF2K and cyclin D1 signaling to support TNBC cell proliferation, thus inhibition of 5-HT7/FOXM1 signaling may be used as a potential therapeutic strategy for targeting TNBC.

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“…Transcription factors (TF) act as additional gene regulators that can bind to DNA and control transcriptional activation or repression (13,14). Numerous studies have shown that TFs further regulate miRNA expression by binding to miRNA promoters (15)(16)(17)(18)(19). For example, transcription factor pu.1 activates miR-424 by binding to its promoter to encourage human macrophage differentiation (20).…”

Section: Introductionmentioning

confidence: 99%

elk1/miR-462-731 Feedback Loop Regulates Macrophages Polarization and Phagocytosis in Grass Carp (Ctenopharyngodon idella)

Liu

Yue

et al. 2022

Front. Immunol.

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MicroRNA clusters are microRNAs (miRNAs) that are distributed in close proximity on chromosomes. In this study, we report a miRNA cluster identified from grass carp (Ctenopharyngodon idella), miR-462-731, which plays a positive role in host antibacterial immunity. The expression of miR-462-731 was disrupted after infection by Aeromonas hydrophila. Transcription factor ETS transcription factor ELK1 was identified to bind to the promoter of the miR-462-731 cluster and suppress its expression. In addition, miR-731 negatively regulates the expression of elk1, forms an elk1/miR-462-731 double negative feedback loop. In addition, we found that miR-731 directly targets ezrin a (ezra), participates in inducing PI3K/AKT signaling in macrophage, to induce macrophage polarization to the M1 phenotype with stronger phagocytosis. Our results demonstrate a novel elk1/miR-462-731 feedback loop. The data deepen our understanding of the relationship between macrophage polarization and phagocytosis in teleost fish.

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MicroRNA profiling identifies Forkhead box transcription factor M1 (FOXM1) regulated miR-186 and miR-200b alterations in triple negative breast cancer

Cited by 18 publications

References 78 publications

FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

Serotonin 5-HT7 Receptor Is A Biomarker Poor Prognostic Factor And Induces Proliferation of Triple Negative Breast Cancer Cells Through FOXM1

elk1/miR-462-731 Feedback Loop Regulates Macrophages Polarization and Phagocytosis in Grass Carp (Ctenopharyngodon idella)

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