Effects of treatment with androgen receptor ligands on microRNA expression of prostate cancer cells

Segal, Corrinne V.; Koufaris, Costas; Powell, Chris J.; Gooderham, Nigel J.

doi:10.1016/j.tox.2015.04.002

Cited by 12 publications

(8 citation statements)

References 31 publications

(16 reference statements)

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“…Indeed, recent studies showed that although DHT and mibolerone are non-aromatizable androgens, mibolerone may have distinct non-physiological effects on the cell's molecular signaling machinery, such as that mibolerone can activate progestin receptors in breast cancer cells, a non-physiological effect that DHT does not exhibit (Cops et al, 2008 ). Similarly, the expression of some miRNAs in LNCaP cells, such as miR-120 can be induced in the presence of mibolerone, but not DHT (Segal et al, 2015 ). Taken together, we hypothesize that AR recruitment to the Fgf8 promoter under normal physiological conditions is independent of the cellular and extracellular androgen milieu, however a more extensive analysis of AR/ARE function are needed to definitively rule out an androgen-mediated effect on Fgf8 expression.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen-Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases

Linscott

Chung

2016

Front. Cell Dev. Biol.

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Fibroblast growth factor 8 (FGF8) is a potent morphogen that regulates the embryonic development of hypothalamic neuroendocrine cells. Indeed, using Fgf8 hypomorphic mice, we showed that reduced Fgf8 mRNA expression completely eliminated the presence of gonadotropin-releasing hormone (GnRH) neurons. These findings suggest that FGF8 signaling is required during the embryonic development of mouse GnRH neurons. Additionally, in situ hybridization studies showed that the embryonic primordial birth place of GnRH neurons, the olfactory placode, is highly enriched for Fgf8 mRNA expression. Taken together these data underscore the importance of FGF8 signaling for GnRH emergence. However, an important question remains unanswered: How is Fgf8 gene expression regulated in the developing embryonic mouse brain? One major candidate is the androgen receptor (AR), which has been shown to upregulate Fgf8 mRNA in 60–70% of newly diagnosed prostate cancers. Therefore, we hypothesized that ARs may be involved in the regulation of Fgf8 transcription in the developing mouse brain. To test this hypothesis, we used chromatin-immunoprecipitation (ChIP) assays to elucidate whether ARs interact with the 5′UTR region upstream of the translational start site of the Fgf8 gene in immortalized mouse GnRH neurons (GT1-7) and nasal explants. Our data showed that while AR interacts with the Fgf8 promoter region, this interaction was androgen-independent, and that androgen treatment did not affect Fgf8 mRNA levels, indicating that androgen signaling does not induce Fgf8 transcription. In contrast, inhibition of DNA methyltransferases (DNMT) significantly upregulated Fgf8 mRNA levels indicating that Fgf8 transcriptional activity may be dependent on DNA methylation status.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen-Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases

Linscott

Chung

2016

Front. Cell Dev. Biol.

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“…Levels of miR‐1290 in the serum have been reported to be able to distinguish pancreatic cancer patients from healthy and disease controls . Expression of miR‐1290 is also decreased in prostate cancer cells treated with androgen receptor ligands .…”

Section: Hsm and Psm Are Reported To Act As Oncogenesmentioning

confidence: 99%

Human and primate‐specific microRNAs in cancer: Evolution, and significance in comparison with more distantly‐related research models

Koufaris

2016

BioEssays

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The largest proportion of microRNAs in humans (ca. 40-50%) originated in the phylogenetic grouping defined as primates. The dynamic evolution of this family of non-coding RNA is further demonstrated by the presence of microRNA unique to the human species. Investigations into the role of microRNA in cancer have until recently mainly focused on the more ancient members of this RNA family that are widely conserved in the animal kingdom. As I describe in this review the evolutionary young lineage and species-specific microRNA could be important contributors to cancers, especially in particular organs in primates compared to more distantly-related research models. Elucidating the biological significance of primate and human-specific microRNA in cancer could have important implications for cancer research and the use of non-primate animal models.

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“…AR would mediate the downregulation of miR-221/miR-222 in CRPC (Gui, Hsieh, Kantoff, Kibel, & Jia, 2017). Moreover, AR agonists can also repress miR-221, which is involved in PCa development (Segal, Koufaris, Powell, & Gooderham, 2015).…”

Section: Androgen Receptormentioning

confidence: 98%

Androgen receptor‐related micro RNAs in prostate cancer and their role in antiandrogen drug resistance

Rezaei

Mahjoubin‐Tehran

Sahebkar

et al. 2019

Journal Cellular Physiology

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Prostate cancer (PCa) is one of the most common cancers and the fifth most common reason for cancer deaths in the males. Surgical castration combined with androgen deprivation therapy, antiandrogens, and androgen synthesis inhibitors is the current therapeutic modalities for PCa. These strategies inhibit androgen synthesis or reduce its binding to the androgen receptor (AR) but the development of resistance to these therapies and transient responsiveness are challenging issues in the treatment of this cancer. Deregulation of ARs has a vital role in the initiation and progression of PCa. Also, recent findings imply that micro RNAs (miRNAs) are involved in the evolution of PCa and mediate drug resistance in different cancers. Hence, discovering and targeting miRNAs might represent a novel therapeutic approach. This review paid particular attention to the AR pathway and existing information on the possible roles of miRNAs associated with AR pathway and drug resistance to two second-generation antiandrogens, that is, enzalutamide and abiraterone.

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Effects of treatment with androgen receptor ligands on microRNA expression of prostate cancer cells

Cited by 12 publications

References 31 publications

Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen-Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases

Fibroblast Growth Factor 8 Expression in GT1-7 GnRH-Secreting Neurons Is Androgen-Independent, but Can Be Upregulated by the Inhibition of DNA Methyltransferases

Human and primate‐specific microRNAs in cancer: Evolution, and significance in comparison with more distantly‐related research models

Androgen receptor‐related micro RNAs in prostate cancer and their role in antiandrogen drug resistance

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