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  1. Article ; Online: Author Correction

    Jiawei Zhao / Eunice E. Lee / Jiwoong Kim / Rong Yang / Bahir Chamseddin / Chunyang Ni / Elona Gusho / Yang Xie / Cheng-Ming Chiang / Michael Buszczak / Xiaowei Zhan / Laimonis Laimins / Richard C. Wang

    Nature Communications, Vol 13, Iss 1, Pp 1-

    Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus

    2022  Volume 1

    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: BRD4 inhibition and FXR activation, individually beneficial in cholestasis, are antagonistic in combination

    Hyunkyung Jung / Jinjing Chen / Xiangming Hu / Hao Sun / Shwu-Yuan Wu / Cheng-Ming Chiang / Byron Kemper / Lin-Feng Chen / Jongsook Kim Kemper

    JCI Insight, Vol 6, Iss

    2021  Volume 1

    Abstract: Activation of farnesoid X receptor (FXR) by obeticholic acid (OCA) reduces hepatic inflammation and fibrosis in patients with primary biliary cholangitis (PBC), a life-threatening cholestatic liver failure. Inhibition of bromodomain-containing protein 4 ( ...

    Abstract Activation of farnesoid X receptor (FXR) by obeticholic acid (OCA) reduces hepatic inflammation and fibrosis in patients with primary biliary cholangitis (PBC), a life-threatening cholestatic liver failure. Inhibition of bromodomain-containing protein 4 (BRD4) also has antiinflammatory, antifibrotic effects in mice. We determined the role of BRD4 in FXR function in bile acid (BA) regulation and examined whether the known beneficial effects of OCA are enhanced by inhibiting BRD4 in cholestatic mice. Liver-specific downregulation of BRD4 disrupted BA homeostasis in mice, and FXR-mediated regulation of BA-related genes, including small heterodimer partner and cholesterol 7 alpha-hydroxylase, was BRD4 dependent. In cholestatic mice, JQ1 or OCA treatment ameliorated hepatotoxicity, inflammation, and fibrosis, but surprisingly, was antagonistic in combination. Mechanistically, OCA increased binding of FXR, and the corepressor silencing mediator of retinoid and thyroid hormone receptor (SMRT) decreased NF-κB binding at inflammatory genes and repressed the genes in a BRD4-dependent manner. In patients with PBC, hepatic expression of FXR and BRD4 was significantly reduced. In conclusion, BRD4 is a potentially novel cofactor of FXR for maintaining BA homeostasis and hepatoprotection. Although BRD4 promotes hepatic inflammation and fibrosis in cholestasis, paradoxically, BRD4 is required for the antiinflammatory, antifibrotic actions of OCA-activated FXR. Cotreatment with OCA and JQ1, individually beneficial, may be antagonistic in treatment of liver disease patients with inflammation and fibrosis complications.
    Keywords Hepatology ; Inflammation ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Involvement of Brd4 in different steps of the papillomavirus life cycle

    Iftner, Thomas / Juliane Haedicke-Jarboui / Shwu-Yuan Wu / Cheng-Ming Chiang

    Virus research. 2017 Mar. 02, v. 231

    2017  

    Abstract: Bromodomain-containing protein 4 (Brd4) is a cellular chromatin-binding factor and transcriptional regulator that recruits sequence-specific transcription factors and chromatin modulators to control target gene transcription. Papillomaviruses (PVs) have ... ...

    Abstract Bromodomain-containing protein 4 (Brd4) is a cellular chromatin-binding factor and transcriptional regulator that recruits sequence-specific transcription factors and chromatin modulators to control target gene transcription. Papillomaviruses (PVs) have evolved to hijack Brd4’s activity in order to create a facilitating environment for the viral life cycle. Brd4, in association with the major viral regulatory protein E2, is involved in multiple steps of the PV life cycle including replication initiation, viral gene transcription, and viral genome segregation and maintenance. Phosphorylation of Brd4, regulated by casein kinase II (CK2) and protein phosphatase 2A (PP2A), is critical for viral gene transcription as well as E1- and E2-dependent origin replication. Thus, pharmacological agents regulating Brd4 phosphorylation and inhibitors blocking phospho-Brd4 functions are promising candidates for therapeutic intervention in treating human papillomavirus (HPV) infections as well as associated disease.
    Keywords Papillomaviridae ; chromatin ; genome ; humans ; non-specific serine/threonine protein kinase ; phosphorylation ; regulatory proteins ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2017-0302
    Size p. 76-82.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2016.12.006
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer

    Lung-Hung Tsai / Kai-Wen Hsu / Cheng-Ming Chiang / Hsiu-Ju Yang / Yu-Huei Liu / Shun-Fa Yang / Pei-Hua Peng / Wei-Chung Cheng / Heng-Hsiung Wu

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: Abstract Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug ... ...

    Abstract Abstract Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug resistance. Resistance to nucleoside analog gemcitabine frequently used in first-line therapy is an urgent issue in pancreatic cancer treatment. Expression of mucin (MUC) glycoproteins has been shown to enhance chemoresistance via increased cell stemness. Here we show interlukine-17 receptor B (IL-17RB) expression is positively correlated with MUC1 and MUC4 expression in pancreatic cancer cells and tumor tissue. Moreover, IL-17RB transcriptionally up-regulates expression of MUC1 and MUC4 to enhance cancer stem-like properties and resistance to gemcitabine. These results suggest IL-17RB can be a potential target for pancreatic cancer therapy. Indeed, treatment with IL-17RB-neutralizing antibody has a synergistic effect in combination with gemcitabine for killing pancreatic cancer cells. Altogether, these findings provide feasible applications for IL-17RB-targeting therapy in pancreatic cancer treatment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus

    Jiawei Zhao / Eunice E. Lee / Jiwoong Kim / Rong Yang / Bahir Chamseddin / Chunyang Ni / Elona Gusho / Yang Xie / Cheng-Ming Chiang / Michael Buszczak / Xiaowei Zhan / Laimonis Laimins / Richard C. Wang

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: The authors identify circular RNAs (circRNA) from human papillomavirus and show that circRNA-encoded E7 contributes to cancer cell growth in vitro and in tumor xenografts. Furthermore, circE7 is present in TCGA RNA-Seq data from HPV-positive cancers. ...

    Abstract The authors identify circular RNAs (circRNA) from human papillomavirus and show that circRNA-encoded E7 contributes to cancer cell growth in vitro and in tumor xenografts. Furthermore, circE7 is present in TCGA RNA-Seq data from HPV-positive cancers.
    Keywords Science ; Q
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus

    Jiawei Zhao / Eunice E. Lee / Jiwoong Kim / Rong Yang / Bahir Chamseddin / Chunyang Ni / Elona Gusho / Yang Xie / Cheng-Ming Chiang / Michael Buszczak / Xiaowei Zhan / Laimonis Laimins / Richard C. Wang

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: The authors identify circular RNAs (circRNA) from human papillomavirus and show that circRNA-encoded E7 contributes to cancer cell growth in vitro and in tumor xenografts. Furthermore, circE7 is present in TCGA RNA-Seq data from HPV-positive cancers. ...

    Abstract The authors identify circular RNAs (circRNA) from human papillomavirus and show that circRNA-encoded E7 contributes to cancer cell growth in vitro and in tumor xenografts. Furthermore, circE7 is present in TCGA RNA-Seq data from HPV-positive cancers.
    Keywords Science ; Q
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

    Shwu-Yuan Wu / Dawn Sijin Nin / A-Young Lee / Scott Simanski / Thomas Kodadek / Cheng-Ming Chiang

    Cell Reports, Vol 16, Iss 6, Pp 1733-

    2016  Volume 1748

    Abstract: Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4), a transcription co-factor and chromatin regulator, uses ... ...

    Abstract Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4), a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV) to viral early gene and cellular matrix metalloproteinase-9 (MMP-9) promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2016-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Targeting ESR1 mutation–induced transcriptional addiction in breast cancer with BET inhibition

    Sm N. Udden / Qian Wang / Sunil Kumar / Venkat S. Malladi / Shwu-Yuan Wu / Shuguang Wei / Bruce A. Posner / Sophie Geboers / Noelle S. Williams / Yulun Liu / Jayesh K. Sharma / Ram S. Mani / Srinivas Malladi / Karla Parra / Mia Hofstad / Ganesh V. Raj / Jose M. Larios / Reshma Jagsi / Max S. Wicha /
    Ben Ho Park / Gaorav P. Gupta / Arul M. Chinnaiyan / Cheng-Ming Chiang / Prasanna G. Alluri

    JCI Insight, Vol 7, Iss

    2022  Volume 17

    Abstract: Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is ... ...

    Abstract Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is associated with development of resistance to most endocrine therapies used to treat breast cancer. Employing a high-throughput screen of nearly 1,200 Federal Drug Administration–approved (FDA-approved) drugs, we show that OTX015, a bromodomain and extraterminal domain (BET) inhibitor, is one of the top suppressors of ESR1 mutant cell growth. OTX015 was more efficacious than fulvestrant, a selective ER degrader, in inhibiting ESR1 mutant xenograft growth. When combined with abemaciclib, a CDK4/6 inhibitor, OTX015 induced more potent tumor regression than current standard-of-care treatment of abemaciclib + fulvestrant. OTX015 has preferential activity against Y537S mutant breast cancer cells and blocks their clonal selection in competition studies with WT cells. Thus, BET inhibition has the potential to both prevent and overcome ESR1 mutant–induced endocrine therapy resistance in breast cancer.
    Keywords Oncology ; Medicine ; R
    Subject code 616 ; 610
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Time series modeling of cell cycle exit identifies Brd4 dependent regulation of cerebellar neurogenesis

    Clara Penas / Marie E. Maloof / Vasileios Stathias / Jun Long / Sze Kiat Tan / Jose Mier / Yin Fang / Camilo Valdes / Jezabel Rodriguez-Blanco / Cheng-Ming Chiang / David J. Robbins / Daniel J. Liebl / Jae K. Lee / Mary E. Hatten / Jennifer Clarke / Nagi G. Ayad

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: The mechanisms controlling irreversible cell cycle exit in cerebellar granule progenitors (GCPs) have not been fully elucidated. Here, the authors performed RNA-sequencing of GCPs exiting the cell cycle to identify downregulation of Brd4 activity as an ... ...

    Abstract The mechanisms controlling irreversible cell cycle exit in cerebellar granule progenitors (GCPs) have not been fully elucidated. Here, the authors performed RNA-sequencing of GCPs exiting the cell cycle to identify downregulation of Brd4 activity as an early event during cell cycle exit which subsequently regulates Shh activity and is needed for proper cerebellar development
    Keywords Science ; Q
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Time series modeling of cell cycle exit identifies Brd4 dependent regulation of cerebellar neurogenesis

    Clara Penas / Marie E. Maloof / Vasileios Stathias / Jun Long / Sze Kiat Tan / Jose Mier / Yin Fang / Camilo Valdes / Jezabel Rodriguez-Blanco / Cheng-Ming Chiang / David J. Robbins / Daniel J. Liebl / Jae K. Lee / Mary E. Hatten / Jennifer Clarke / Nagi G. Ayad

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: The mechanisms controlling irreversible cell cycle exit in cerebellar granule progenitors (GCPs) have not been fully elucidated. Here, the authors performed RNA-sequencing of GCPs exiting the cell cycle to identify downregulation of Brd4 activity as an ... ...

    Abstract The mechanisms controlling irreversible cell cycle exit in cerebellar granule progenitors (GCPs) have not been fully elucidated. Here, the authors performed RNA-sequencing of GCPs exiting the cell cycle to identify downregulation of Brd4 activity as an early event during cell cycle exit which subsequently regulates Shh activity and is needed for proper cerebellar development
    Keywords Science ; Q
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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