Definition of a FoxA1 Cistrome That Is Crucial for G1 to S-Phase Cell-Cycle Transit in Castration-Resistant Prostate Cancer

Zhang, Chunpeng; Wang, Liguo; Wu, Dayong; Chen, Hongyan; Chen, Zhong; Thomas‐Ahner, Jennifer M.; Zynger, Debra L.; Eeckhoute, Jérôme; Yu, Jindan; Luo, Jun; Brown, Myles; Clinton, Steven K.; Nephew, Kenneth P.; Huang, Tim H.M.; Li, Wei; Wang, Qianben

doi:10.1158/0008-5472.can-11-1882

Cited by 84 publications

(96 citation statements)

References 45 publications

(65 reference statements)

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“…All four databases (microRNA.org, miRWalk, DIANA and TargetScan) predicted that its expression was correlated with levels of miR-204. FOXA1 has been reported to play an essential role in cell proliferation (26), the cell cycle (27), DNA methylation (28) and tumor development and progression (21). We therefore focused on the relationship between miR-204 and FOXA1.…”

Section: Mir-204 Target Gene Predictions Foxa1 a Transcriptionmentioning

confidence: 99%

miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1

et al. 2017

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Abstract. MicroRNAs (miRNAs) are short, non-proteincoding RNAs and transcripts that are 18-24 nt in length. miR-204 was first identified as an anti-oncogene and is reported to be downregulated in non-small cell lung cancer, glioma, gastric and thyroid cancer. Recent studies have proposed that a low level of miR-204 expression is associated with tumor progression and disease outcome in breast cancer. Forkhead box A1 (FOXA1), a transcription factor, plays a crucial role in breast cancer and has been predicted as a target of miR-204. In the present study, we integrated the results of microarray analyses of breast cancer tissues obtained from an online database with our own determination of the expression of miR-204 in breast cancer MCF-7 cells using real-time qPCR (RT-qPCR). The proliferative capacity of the cells was assessed using MTT assays, and cell mobility and invasiveness were evaluated using cell migration and invasion assays, respectively. Flow cytometry was used to analyze apoptosis. FOXA1 levels were detected using RT-qPCR and western blot analysis. Luciferase assays were performed to confirm that FOXA1 is directly targeted by miR-204. The results showed that miR-204 was downregulated in breast cancer cells, and we found that miR-204 was expressed at a lower level in MCF-7 cells than that observed in normal breast epithelial HBL-100 cells. Overexpression of miR-204 inhibited cell proliferation, migration and invasion and promoted apoptosis. Western blot analysis revealed that the expression of FOXA1 at the protein level was significantly reduced after cells were transfected with miR-204-expressing viruses. Luciferase assays demonstrated that FOXA1 is a direct target of miR-204, which binds to FOXA1 in a complementary region. In conclusion, miR-204 regulates the biological behavior of breast cancer cells, including cell proliferation, invasion, metastasis and apoptosis, by directly targeting FOXA1. Thus, miR-204 may act as a tumor-suppressor, and the results of the present study provide a reference for future research into the potential mechanisms underlying breast cancer progression.

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Section: Mir-204 Target Gene Predictions Foxa1 a Transcriptionmentioning

confidence: 99%

miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1

et al. 2017

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“…For example, the concerted upregulation of IL-8 by FOXA1 and ER in endocrine therapy-resistant BCa cells identifies a potential target for the treatment of ER-positive, FOXA1-high patients (104). Moreover, FOXA1 also drives proliferation in PCa and BCa cell lines (100,106), suggesting that it can also be considered as a therapeutic target. It is possible that compounds selectively targeting FOXA1 may be identified since the transcriptional activity of a related factor, FOXM1, can be inhibited by a small molecule (107).…”

Section: R E V I E W S E R I E S : N U C L E a R R E C E P T O R Smentioning

confidence: 99%

Role of steroid receptor and coregulator mutations in hormone-dependent cancers

Groner¹,

Brown²

2017

Journal of Clinical Investigation

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“…10 FOXA1 controls AR and estrogen receptor (ER) regulated hormones in prostate cancer cells and breast cancer cells, respectively. 10 Although only 5 of 147 (3.4%) screened prostate cancer lines showed FOXA1 mutation, these mutations in an AR cofactor are important due to the crucial role of AR in CRPC signaling. 3 Further, the authors showed siRNA knockdown of FOXA1 yields decreased growth in LNCaP cells.…”

Section: Notementioning

confidence: 99%

“…3 Further, the authors showed siRNA knockdown of FOXA1 yields decreased growth in LNCaP cells. 3,10 While we have made significant strides in understanding the biology of prostate cancer over the past 25 years, much knowledge of the spectrum of prostate ETS1 activity marks poor prognosis and conveys abnormal regulation of many cancer-linked genes. This poor transcriptional regulation results in enhanced cell survival, cell growth, angiogenesis, migration and invasion.…”

Section: Notementioning

confidence: 99%