Scholars@Duke
Qianben Wang

Qianben Wang

Banks Anderson, Sr. Distinguished Professor
Pathology
qianben.wang@duke.edu
Room 1027A, GSRB1, Box #103864,, Durham, NC 27710

Selected Publications

Integrative analysis identifies the atypical repressor E2F8 as a targetable transcriptional activator driving lethal prostate cancer.

Journal Article Oncogene · November 2024 Acquired resistance to androgen receptor (AR)-targeted therapies underscores the need to identify alternative therapeutic targets for treating lethal prostate cancer. In this study, we evaluated the prognostic significance of 1635 human transcription facto ... Full text Cite

Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions.

Journal Article Mol Cell · October 5, 2023 Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates throug ... Full text Link to item Cite

RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis.

Journal Article J Clin Invest · May 15, 2023 Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient ca ... Full text Open Access Link to item Cite

SMAD3 promotes expression and activity of the androgen receptor in prostate cancer.

Journal Article Nucleic Acids Res · April 11, 2023 Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased le ... Full text Link to item Cite

Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches.

Journal Article Front Genome Ed · 2023 Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as ide ... Full text Open Access Link to item Cite

Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

Journal Article Nat Chem Biol · October 2022 SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encap ... Full text Link to item Cite

Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.

Journal Article Nat Commun · June 7, 2022 Knowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome lan ... Full text Open Access Link to item Cite

Phosphorylated MED1 links transcription recycling and cancer growth.

Journal Article Nucleic acids research · May 2022 Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in ... Full text Cite

Dietary omega-3 fatty acid intake impacts peripheral blood DNA methylation -anti-inflammatory effects and individual variability in a pilot study.

Journal Article J Nutr Biochem · January 2022 Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits that may relate to anti-inflammatory activity. However, mechanisms mediating an anti-inflammatory response to n-3 PUFA intake are not fully understood. Of interest is ... Full text Link to item Cite

Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling.

Journal Article Nat Commun · November 3, 2021 RNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putati ... Full text Link to item Cite

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer.

Journal Article Proc Natl Acad Sci U S A · March 30, 2021 Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report ... Full text Link to item Cite

Alternative polyadenylation of mRNA and its role in cancer.

Journal Article Genes Dis · January 2021 Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3' end of RNA polymerase II transcripts from over 60% of human genes. APA is derived from the existence of multiple polyadenylation signals (PAS) within the same trans ... Full text Link to item Cite

Prostate Cancer Cell Phenotypes Remain Stable Following PDE5 Inhibition in the Clinically Relevant Range.

Journal Article Transl Oncol · September 2020 Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate ... Full text Link to item Cite

Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.

Journal Article Cancer Res · June 15, 2020 The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic ... Full text Link to item Cite

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

Journal Article Sci Transl Med · December 4, 2019 Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR- neuroendocrine (NE) ... Full text Link to item Cite

Molecular determinants for enzalutamide-induced transcription in prostate cancer.

Journal Article Nucleic Acids Res · November 4, 2019 Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. ... Full text Open Access Link to item Cite

Loss of tumor suppressor IGFBP4 drives epigenetic reprogramming in hepatic carcinogenesis.

Journal Article Nucleic Acids Res · September 28, 2018 Genomic sequencing of hepatocellular carcinoma (HCC) uncovers a paucity of actionable mutations, underscoring the necessity to exploit epigenetic vulnerabilities for therapeutics. In HCC, EZH2-mediated H3K27me3 represents a major oncogenic chromatin modifi ... Full text Open Access Link to item Cite

Chromatin-associated APC regulates gene expression in collaboration with canonical WNT signaling and AP-1.

Journal Article Oncotarget · July 27, 2018 Mutation of the APC gene occurs in a high percentage of colorectal tumors and is a central event driving tumor initiation in the large intestine. The APC protein performs multiple tumor suppressor functions including negative regulation of the canonical WN ... Full text Open Access Link to item Cite

Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.

Journal Article Proc Natl Acad Sci U S A · June 26, 2018 The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting ther ... Full text Link to item Cite

Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.

Journal Article Cancer Res · February 15, 2018 Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen deprivation therapy. In this study, we investigated this phenomenon by strati ... Full text Link to item Cite

Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.

Journal Article Nucleic Acids Res · September 19, 2016 The compaction of nucleosomal structures creates a barrier for DNA-binding transcription factors (TFs) to access their cognate cis-regulatory elements. Pioneer factors (PFs) such as FOXA1 are able to directly access these cis-targets within compact chromat ... Full text Link to item Cite

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

Journal Article Nucleic Acids Res · May 19, 2016 Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 ... Full text Link to item Cite

Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice.

Journal Article Sci Data · February 16, 2016 E2F3 and MYC are transcription factors that control cellular proliferation. To study their mechanism of action in the context of a regenerating tissue, we isolated both proliferating (crypts) and non-dividing (villi) cells from wild-type and Rb depleted sm ... Full text Link to item Cite

Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.

Journal Article Nat Genet · October 2015 Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs a ... Full text Link to item Cite

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.

Journal Article Nat Commun · September 16, 2015 Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find ... Full text Link to item Cite

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Journal Article Nat Cell Biol · August 2015 Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells ... Full text Link to item Cite

Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer

Journal Article Proceedings of the National Academy of Sciences · May 12, 2015 Significance Papillary thyroid carcinoma (PTC) displays a strong hereditary component that is, in part, due to the additive effects of numerous low-penetrance genes or variants, but virtually no mecha ... Full text Cite

Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

Journal Article EMBO J · February 12, 2015 Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific ... Full text Link to item Cite

Three-tiered role of the pioneer factor GATA2 in promoting androgen-dependent gene expression in prostate cancer.

Journal Article Nucleic Acids Res · April 2014 In prostate cancer, androgen receptor (AR) binding and androgen-responsive gene expression are defined by hormone-independent binding patterns of the pioneer factors FoxA1 and GATA2. Insufficient evidence of the mechanisms by which GATA2 contributes to thi ... Full text Link to item Cite

Knockdown of PRKAR1A, the Gene Responsible for Carney Complex, Interferes With Differentiation in Osteoblastic Cells

Journal Article Molecular Endocrinology · March 1, 2014 AbstractPRKAR1A is the gene encoding the type 1A regulatory subunit of protein kinase A, and it is the cause of the inherited human tumor syndrome Carney complex. Data from our laboratory has demonstrated th ... Full text Cite

Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors.

Journal Article Nucleic Acids Res · March 2014 Alternative splicing (AS), in higher eukaryotes, is one of the mechanisms of post-transcriptional regulation that generate multiple transcripts from the same gene. One particular mode of AS is the skipping event where an exon may be alternatively excluded ... Full text Link to item Cite

S100A14: Novel Modulator of Terminal Differentiation in Esophageal Cancer

Journal Article Molecular Cancer Research · December 1, 2013 AbstractAberrant keratinocyte differentiation is a key mechanism in the initiation of cancer. Because activities regulating differentiation exhibit altered or reduced capacity in esophageal cancer cells, it ... Full text Cite

ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer

Journal Article Journal of Clinical Investigation · March 1, 2013 Full text Cite

Cross-talk between HER2 and MED1 Regulates Tamoxifen Resistance of Human Breast Cancer Cells

Journal Article Cancer Research · November 1, 2012 AbstractDespite the fact that most breast cancer patients have estrogen receptor (ER) α-positive tumors, up to 50% of the patients are or soon develop resistance to endocrine therapy. It is recognized that H ... Full text Cite

Mapping mutations in prostate cancer exomes

Journal Article Asian Journal of Andrology · November 2012 Full text Cite

Integrated analysis identifies a class of androgen-responsive genes regulated by short combinatorial long-range mechanism facilitated by CTCF.

Journal Article Nucleic Acids Res · June 2012 Recently, much attention has been given to elucidate how long-range gene regulation comes into play and how histone modifications and distal transcription factor binding contribute toward this mechanism. Androgen receptor (AR), a key regulator of prostate ... Full text Link to item Cite

Cooperation between Polycomb and androgen receptor during oncogenic transformation

Journal Article Genome Research · February 2012 Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development and function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has bee ... Full text Cite

Androgen receptor-driven chromatin looping in prostate cancer

Journal Article Trends in Endocrinology & Metabolism · December 2011 Full text Cite

Definition of a FoxA1 Cistrome that is crucial for G1 to S-phase cell-cycle transit in castration-resistant prostate cancer.

Journal Article Cancer Res · November 1, 2011 The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G₂ to M-phase cell-cycle ... Full text Link to item Cite

CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability.

Journal Article Cancer Res · July 15, 2011 The cell-cycle G(2)-M phase gene UBE2C is overexpressed in various solid tumors including castration-resistant prostate cancer (CRPC). Our recent studies found UBE2C to be a CRPC-specific androgen receptor (AR) target gene that is necessary for CRPC growth ... Full text Link to item Cite

Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth.

Journal Article EMBO J · May 10, 2011 The UBE2C oncogene is overexpressed in many types of solid tumours including the lethal castration-resistant prostate cancer (CRPC). The underlying mechanisms causing UBE2C gene overexpression in CRPC are not fully understood. Here, we show that CRPC-speci ... Full text Link to item Cite

CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells.

Journal Article Cancer Res · January 15, 2011 While patients with advanced prostate cancer initially respond favorably to androgen ablation therapy, most experience a relapse of the disease within 1-2 years. Although hormone-refractory disease is unresponsive to androgen-deprivation, androgen receptor ... Full text Link to item Cite

Histone modifications and chromatin organization in prostate cancer.

Journal Article Epigenomics · August 2010 Epigenetic mechanisms, including histone modifications, nucleosomal remodeling and chromosomal looping, contribute to the onset and progression of prostate cancer. Recent technical advances significantly increase our understanding of the genome-wide epigen ... Full text Link to item Cite

Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping.

Journal Article Genome Res · June 2010 The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigene ... Full text Link to item Cite

Nucleosome dynamics define transcriptional enhancers

Journal Article Nature Genetics · April 2010 Full text Cite

Induction of Kruppel-like factor 5 expression by androgens results in increased CXCR4-dependent migration of prostate cancer cells in vitro.

Journal Article Mol Endocrinol · September 2009 Advanced prostate cancers preferentially metastasize to bone, suggesting that this tissue produces factors that provide a suitable microenvironment for prostate cancer cells. Recently, it has become clear that even in antiandrogen-resistant cancers, the an ... Full text Link to item Cite

Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.

Journal Article Cell · July 23, 2009 The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. W ... Full text Link to item Cite

The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines

Journal Article Cancer Research · April 15, 2009 AbstractAndrogen-dependent prostate cancer typically progresses to castration-resistant prostate cancer (CRPC) after the androgen deprivation therapy. MicroRNAs (miR) are noncoding small RNAs (19-25nt) that ... Full text Cite

Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

Journal Article Cancer Research · April 1, 2009 AbstractThe androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sit ... Full text Cite

Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase

Journal Article Molecular Endocrinology · November 1, 2008 AbstractEvidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapi ... Full text Cite

Androgen receptor mediates the expression of UDP‐glucuronosyltransferase 2 B15 and B17 genes

Journal Article The Prostate · June 2008 AbstractBACKGROUNDEnhanced androgen receptor (AR) activity by increased testosterone availability may play important roles in prostate cancer progressing to castration resistant state. Com ... Full text Cite

Genome-wide analysis of estrogen receptor binding sites

Journal Article Nature Genetics · November 2006 Full text Cite

Specific Structural Motifs Determine TRAP220 Interactions with Nuclear Hormone Receptors

Journal Article Molecular and Cellular Biology · August 1, 2000 Full text Cite