Article
Nutrition & Dietetics
Sabeeta Kapoor, Elisabetta Damiani, Shan Wang, Ravirajan Dharmanand, Chakrapani Tripathi, Jorge Enrique Tovar Perez, Wan Mohaiza Dashwood, Praveen Rajendran, Roderick Hugh Dashwood
Summary: Epigenetic mechanisms, specifically the deregulation of bromodomain (BRD) functions, play a significant role in colorectal cancer (CRC) and other malignancies. This study shows that overexpression of BRD9 is associated with poor prognostic outcomes in CRC patients. Natural polyphenols such as Epigallocatechin-3-gallate (EGCG), Equol, Quercetin, and Aspalathin were identified as potential BRD9 antagonists, as they reduced colon cancer cell viability, inhibited colony formation, and increased DNA damage and apoptosis.
Article
Biochemistry & Molecular Biology
Jacob Borold, Davide Eletto, Idoia Busnadiego, Nina K. Mair, Eva Moritz, Samira Schiefer, Nora Schmidt, Philipp P. Petric, W. Wei-Lynn Wong, Martin Schwemmle, Benjamin G. Hale
Summary: The study identified BRD9 as a critical factor for IFN-induced ISG expression, and genetic knockout or degradation of BRD9 can limit ISG expression and attenuate the antiviral activity of IFN. BRD9 acts at the transcriptional level through interactions with factors like STAT2, possibly serving as an important regulatory factor for inhibiting ISG expression.
Article
Multidisciplinary Sciences
Liu Wang, Tae Gyu Oh, Jason Magida, Gabriela Estepa, S. M. Bukola Obayomi, Ling-Wa Chong, Jovylyn Gatchalian, Ruth T. Yu, Annette R. Atkins, Diana Hargreaves, Michael Downes, Zong Wei, Ronald M. Evans
Summary: This study identified BRD9 as a modulator of glucocorticoid responses in macrophages. Inhibition or genetic depletion of BRD9 attenuated macrophage responses to inflammatory stimuli. BRD9 inhibitors have the potential to enhance the therapeutic effects of glucocorticoids by potentiating antiinflammatory responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Nasiha S. Ahmed, Jovylyn Gatchalian, Josephine Ho, Mannix J. Burns, Nasun Hah, Zong Wei, Michael Downes, Ronald M. Evans, Diana C. Hargreaves
Summary: This study found that the noncanonical BAF complex (ncBAF), a variant of the SWI/SNF complex, regulates the expression of secondary-response genes in the interferon response pathway. The BRD9 subunit of the ncBAF complex plays a specific role in the activation of interferon-stimulated genes (ISGs). Inhibition of BRD9 led to a reduction in ISG expression following endotoxin stimulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Maria Mushtaq Ali, Sehrish Naz, Sajda Ashraf, Stefan Knapp, Zaheer Ul-Haq
Summary: BRD9 inhibitors have potential therapeutic value in cancer treatment by selectively targeting BRD9 and BRD7 proteins, regulating chromatin structure and gene expression, and inhibiting tumor growth and progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Jingyu Zhang, Haiting Duan, Renzhao Gui, Mingfei Wu, Liteng Shen, Yuheng Jin, Ao Pang, Xiaoli Yu, Shenxin Zeng, Bo Zhang, Nengming Lin, Wenhai Huang, Yuwei Wang, Xiaojun Yao, Jia Li, Xiaowu Dong, Yubo Zhou, Jinxin Che
Summary: This study describes an oral activity BRD9 PROTAC C6 that recruits a highly efficient E3 ligase to degrade BRD9, showing potential therapeutic effects against AML cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Lynda Agbo, Jeremy Loehr, Pata-Eting Kougnassoukou Tchara, Jean-Philippe Lambert
Summary: Bromodomains (BRDs) are important in the recognition of acetylated lysine residues on proteins. In this study, the authors investigated the role of BRD-containing subunits in mSWI/SNF complexes and their impact on transcriptional regulation. They found that loss of a single BRD-containing subunit altered, but did not fully disrupt, the complexes, and downregulation of BRD7 affected the interactome of its homologue BRD9. These findings have implications for targeted therapy of epigenetic regulators in cancer.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Junhua Li, Run Zhu, Xiaoxi Zhuang, Cheng Zhang, Hui Shen, Xishan Wu, Maofeng Zhang, Cen Huang, Qiuping Xiang, Linxiang Zhao, Yong Xu, Yan Zhang
Summary: In this study, a class of novel BET bivalent inhibitors based on a monovalent BET inhibitor 7 (Y06037) was designed, optimized, and evaluated. The representative bivalent inhibitor 17b exhibited 32-fold greater potency in inhibiting cell growth in LNCaP compared to monovalent inhibitor 7. Furthermore, 17b induced 95.1% PSA regression in LNCaP cells at a concentration of 2 μM. Docking study revealed the potential binding mode of 17b with two BET bromodomains. These findings suggest that 17b (Y13021) is a promising BET bivalent inhibitor for the treatment of prostate cancer.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Lawrence David Mason, Suresh Chava, Kiran Kumar Reddi, Romi Gupta
Summary: Melanoma is a deadly form of skin cancer with limited treatment options. This study identified TP-472 as a potential effective therapeutic agent for melanoma by blocking cancer-promoting signaling pathways and inducing cell death. Further research is needed to explore the full potential of TP-472 in melanoma therapy.
Article
Biochemical Research Methods
Lynda Agbo, Jeremy Loehr, Pata-Eting Kougnassoukou Tchara, Jean-Philippe Lambert
Summary: Bromodomains are important protein domains that recognize and read acetylated lysine residues, playing a role in transcriptional regulation. This study reveals the impact of BRD-containing subunits of the mSWI/SNF complex on transcriptional regulation, and the significance of BRD7 downregulation in invasive lobular carcinoma. These findings highlight the interconnectedness of mSWI/SNF complexes and their relevance to transcriptional regulation in human health and disease.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Oncology
Tupa Basuroy, Megan Dreier, Caitlin Baum, Thomas Blomquist, Robert Trumbly, Fabian Filipp, Ivana L. de la Serna
Summary: Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure, and the BRD9 protein promotes melanocyte pigmentation while its pharmacological inhibition leads to repression of melanin synthesis and pigmentation.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Tian-bang Wu, Qiu-ping Xiang, Chao Wang, Chun Wu, Cheng Zhang, Mao-feng Zhang, Zhao-xuan Liu, Yan Zhang, Lin-jiu Xiao, Yong Xu
Summary: In this study, a novel selective BET inhibitor, 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative, was designed, synthesized, and demonstrated to have potent inhibitory effects on prostate cancer cells with high selectivity. This molecule, represented by compound 19 (Y06014), showed promising potential as a small molecule probe for further validation of BET as a molecular target for PC drug development.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Chemistry, Medicinal
Xuetao Chen, Fanying Meng, Jingtian Zhang, Zijian Zhang, Xuan Ye, Weikun Zhang, Yuanyuan Tong, Xinrui Ji, Rujun Xu, Xiao-Li Xu, Qi-Dong You, Zheng-Yu Jiang
Summary: Sepsis is a global health problem and BRD4 inhibitor 27 could be a potential candidate for sepsis treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Derek Lee, Misty Shuo Zhang, Felice Ho-Ching Tsang, Macus Hao-Ran Bao, Iris Ming-Jing Xu, Robin Kit-Ho Lai, David Kung-Chun Chiu, Aki Pui-Wah Tse, Cheuk-Ting Law, Cerise Yuen-Ki Chan, Vincent Wai-Hin Yuen, Noreen Nog-Qin Chui, Irene Oi-Lin Ng, Chun-Ming Wong, Carmen Chak-Lui Wong
Summary: This study reveals the distinct regulatory mechanisms of malic enzymes ME1 and ME3 in hepatocellular carcinoma (HCC), with ME1 being controlled by the NRF2-mediated oxidative stress response pathway and ME3 being constitutively induced by superenhancers. Disrupting these regulatory pathways can slow down HCC progression, and targeting both mechanisms may present a potential therapeutic approach for HCC treatment.
Article
Chemistry, Medicinal
Matthew D. Hill, Haiquan Fang, Derek Norris, George Delucca, Hong Huang, Mikkel DeBenedetto, Claude Quesnelle, William D. Schmitz, John S. Tokarski, Steven Sheriff, Chunhong Yan, Caroline Fanslau, Zuzana Haarhoff, Christine Huang, Melissa Kramer, Shilpa Madari, Krista Menard, Laura Monereau, John Morrison, Nirmala Raghavan, Eric E. Shields, Jean Simmermacher-Mayer, Michael Sinz, Ching Kim Tye, Richard Westhouse, Chunshan Xie, Haiying Zhang, Lisa Zhang, Tatyana Zvyaga, Francis Lee, Ashvinikumar Gavai, Andrew P. Degnan
Summary: This paper describes the synthesis of triazole-containing carboline derivatives and their use as bromodomain and extra-terminal (BET) inhibitors. Detailed investigations of deuteration and fluorination strategies were conducted to reduce clearance while maintaining a favorable in vitro profile. The study identified a potent BET inhibitor, 2-{8-fluoro-3-[4-(H-2(3))methyl-1-methyl-1H-1,2,3-triazol-5-yl]-5-[(S)-(oxan-4-yl)(phenyl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol (15), which exhibited reduced clearance and improved pharmacokinetic (PK) profile in preclinical species.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Engineering, Biomedical
Xiaoli Xu, Lunkun Ma, Yanjiao Wu, Liling Tang
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2018)
Review
Cell & Tissue Engineering
Ying Chen, Liling Tang
CURRENT STEM CELL RESEARCH & THERAPY
(2019)
Review
Cell Biology
Huifang Sun, Jianguo Feng, Liling Tang
Article
Pathology
Yi Zhang, Binyong Liang, Xinhua Song, Haichuan Wang, Matthias Evert, Yi Zhou, Diego F. Calvisi, Liling Tang, Xin Chen
Summary: Loss of Apc alone does not drive liver tumor formation, but synergizes with activated oncogenes (YapS127A, TazS89A, and c-Met) to induce hepatocarcinogenesis. A subset of HCC patients with loss-of-function APC mutations might benefit from therapeutic strategies targeting the Wnt/B-catenin pathway.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Genetics & Heredity
Jianguo Feng, Xichao Xu, Xin Fan, Qian Yi, Liling Tang
Summary: The study reveals that the alternative splicing of Cyclin D1 is altered in cells under mechanical stress, with SRSF1 and BAF57/SMARCE1 potentially serving as critical regulators of this process.
Review
Biotechnology & Applied Microbiology
Rongxue Wan, Jianguo Feng, Liling Tang
Summary: SMAD4 is a typical tumor suppressor gene in the TGF-beta signaling pathway, frequently mutated and inactivated in human cancers, leading to negative consequences, inhibition of tumor growth suppression, and support of tumor progression.
ONCOTARGETS AND THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Piaoyang Liu, Shun Li, Liling Tang
Summary: NGF plays a crucial role in the occurrence and development of various lung diseases by changing protein expression levels and mediating cell function. Anti-NGF may be used in future therapeutic strategies for lung diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Xv Zhang, Liling Tang, Qian Yi
Summary: Insufficient vascularization and maturation hinder the application of stem cell-derived liver organoids. Reviewing theories on the origin of hepatic cells and the morphogenesis of hepatic vessels provides potential approaches for organoid generation. Major protocols for generating vascularized liver organoids from stem cells are considered for their potential and limitations.
Review
Biochemistry & Molecular Biology
Yuanyuan Liang, Shun Li, Liling Tang
Summary: MicroRNAs, specifically the miR-320 family, play a crucial role in regulating gene expression and have been identified as tumor suppressors. Their functions in cancer research extend to inhibition of epithelial-mesenchymal transition, cell proliferation, and apoptosis, while also serving as potential biomarkers for cancer diagnosis and prognosis.
Review
Biochemistry & Molecular Biology
Qiuxia Wang, Jianguo Feng, Liling Tang
Summary: Advancements in high-throughput sequencing and chromatin state mapping have revealed the production of non-coding transcripts/RNAs in eukaryotic cells. Some of these non-coding RNAs have been strongly associated with the development of cancer. The mitogen-activated protein kinases (MAPK) are a family of serine-threonine kinases that play a crucial role in cell signaling from the cell surface to the nucleus. Certain non-coding RNAs associated with the MAPK signaling pathway have been found to play significant roles in the development of various malignancies, including liver cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Wei Mao, Yi Liao, Liling Tang
Summary: Long non-coding RNAs (lncRNAs) have been shown to play important regulatory roles in human cancers, and LINC00173, as a recently discovered non-coding gene, is dysregulated in 11 human cancers and closely associated with biological processes such as proliferation, migration, and invasion.
Review
Biology
Lunkun Ma, Ankit Gilani, Qian Yi, Liling Tang
Summary: Thermogenesis plays a significant role in combating metabolic disorders and obesity, and microRNAs are involved in regulating adipose thermogenesis. This review discusses the diverse roles of microRNAs in adipose thermogenesis and their potential as a target for obesity treatment. Recommendations for future research and miRNA-based therapies for obesity are highlighted.
Review
Biochemistry & Molecular Biology
Qiying Pei, Qian Yi, Liling Tang
Summary: The liver is vital for metabolism and is susceptible to injuries, leading to liver fibrosis which can cause serious health issues. Effective anti-fibrotic medications are lacking, and the current approach of eliminating causes is slow and not always feasible. Understanding the mechanisms of liver fibrosis is crucial for finding new therapeutic targets. Inhibiting hepatic stellate cell activation and related signaling pathways can reverse fibrosis. This review focuses on the activation of hepatic stellate cells and targeting them or liver fibrosis signaling pathways for resolution. Additionally, new therapeutic compounds for liver fibrosis are summarized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Lu Zhang, Yi Zhang, Dongliang Shen, Ying Chen, Jianguo Feng, Xing Wang, Lunkun Ma, Yi Liao, Liling Tang
Summary: Our study found that RBM3 is highly expressed in hepatocellular carcinoma (HCC) tissues and is negatively correlated with patient prognosis. RBM3 overexpression promotes migration and invasion of HCC cells and activates the STAT3 signaling pathway to induce epithelial-mesenchymal transition (EMT). RBM3 expression is inhibited by microRNA-383, and inhibition of RBM3 improves the malignant phenotype of HCC.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2022)
