Androgen Receptor-Mediated Transcription in Prostate Cancer

Özturan, Doğancan; Morova, Tunç; Lack, Nathan A.

doi:10.3390/cells11050898

Cited by 17 publications

(8 citation statements)

References 217 publications

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“…A higher value of s k indicates a greater likelihood of binding of the k-th TF at that specific location in the sequence. TF motifs MA0007.2.AR, MA0148.3.FOXA1, and MA0901.1.HOXB13 [22], were chosen for the AR enhancers regions as they are known to be involved in AR enhancer regulation [23][24][25].…”

Section: Motif Identificationmentioning

confidence: 99%

Inference of Transcriptional Regulation From STARR-seq Data

Safaeesirat,

Taeb,

Tekoglu

et al. 2024

Preprint

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One of the primary regulatory processes in cells is transcription, during which RNA polymerase II (Pol-II) transcribes DNA into RNA. The binding of Pol-II to its site is regulated through interactions with transcription factors (TFs) that bind to DNA at enhancer cis-regulatory elements. Measuring the enhancer activity of large libraries of distinct DNA sequences is now possible using Massively Parallel Reporter Assays (MPRAs), and computational methods have been developed to identify the dominant statistical patterns of TF binding within these large datasets. Such methods are global in their approach and may overlook important regulatory sites which function only within the local context. Here we introduce a method for inferring functional regulatory sites (their number, location and width) within an enhancer sequence based on measurements of its transcriptional activity from an MPRA method such as STARR-seq. The model is based on a mean-field thermodynamic description of Pol-II binding that includes interactions with bound TFs. Our method applied to simulated STARR-seq data for a variety of enhancer architectures shows how data quality impacts the inference and also how it can find local regulatory sites that may be missed in a global approach. We also apply the method to recently measured STARR-seq data on androgen receptor (AR) bound sequences, a TF that plays an important role in the regulation of prostate cancer. The method identifies key regulatory sites within these sequences which are found to overlap with binding sites of known co-regulators of AR.

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Section: Motif Identificationmentioning

confidence: 99%

Inference of Transcriptional Regulation From STARR-seq Data

Safaeesirat,

Taeb,

Tekoglu

et al. 2024

Preprint

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“…The high occurrence of prostate cancer and the implication of the AR signaling in its growth [ 124 , 138 ] resulted in the need to find drugs able to sustain most of the anabolic and protein-protective functions of T because of the limited (or counterproductive) benefits of T deprivation [ 139 , 140 , 141 , 142 ]. These efforts resulted in the development of a large number of selective AR modulators (SARM) [ 143 , 144 ].…”

Section: Mechanisms Of Action Of Androgensmentioning

confidence: 99%

The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health

Alemany

2022

IJMS

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Androgens are an important and diverse group of steroid hormone molecular species. They play varied functional roles, such as the control of metabolic energy fate and partition, the maintenance of skeletal and body protein and integrity and the development of brain capabilities and behavioral setup (including those factors defining maleness). In addition, androgens are the precursors of estrogens, with which they share an extensive control of the reproductive mechanisms (in both sexes). In this review, the types of androgens, their functions and signaling are tabulated and described, including some less-known functions. The close interrelationship between corticosteroids and androgens is also analyzed, centered in the adrenal cortex, together with the main feedback control systems of the hypothalamic–hypophysis–gonads axis, and its modulation by the metabolic environment, sex, age and health. Testosterone (T) is singled out because of its high synthesis rate and turnover, but also because age-related hypogonadism is a key signal for the biologically planned early obsolescence of men, and the delayed onset of a faster rate of functional losses in women after menopause. The close collaboration of T with estradiol (E2) active in the maintenance of body metabolic systems is also presented Their parallel insufficiency has been directly related to the ravages of senescence and the metabolic syndrome constellation of disorders. The clinical use of T to correct hypoandrogenism helps maintain the functionality of core metabolism, limiting excess fat deposition, sarcopenia and cognoscitive frailty (part of these effects are due to the E2 generated from T). The effectiveness of using lipophilic T esters for T replacement treatments is analyzed in depth, and the main problems derived from their application are discussed.

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“…AR functions as a transcription factor in canonical signaling pathway and over 250 co-regulators (co-activators or co-repressors) have been shown to contribute to the regulation of AR transcriptional activity [101,102]. The term AR co-regulators represents a wide group of molecules that include proteins and RNAs that regulate AR activity [72] and the relationship between AR and co-regulators affects development, progression, and treatment outcome of PCa [103].…”

Section: Adt In the Treatment Of Advanced Pcamentioning

confidence: 99%

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Varisli¹,

TOLAN²,

CEN³

et al. 2022

Oncology Research

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Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries. Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years. The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling. Although a partly remediation is accomplished at the beginning of treatment, some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching, from E-cadherin to Ncadherin, which is the hallmark of epithelial-mesenchymal transition. Diverse direct and indirect mechanisms are involved in this switching and consequently, the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells. Since E-cadherin represses invasive and migrative behaviors of the tumor cells, the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation. In this study, we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-β pathway.

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Androgen Receptor-Mediated Transcription in Prostate Cancer

Cited by 17 publications

References 217 publications

Inference of Transcriptional Regulation From STARR-seq Data

Inference of Transcriptional Regulation From STARR-seq Data

The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

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