Article
Biochemistry & Molecular Biology
Yulong Song, Xiuju He, Wenbing Yang, Yaoxing Wu, Jun Cui, Tian Tang, Rui Zhang
Summary: This study developed an editing identification pipeline specifically for RNA viruses and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2 from diverse samples. The findings showed that A-to-I editing was dynamically regulated, varied between tissue and cell types, and correlated with the intensity of innate immune response. Additionally, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. The study also provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans during the epidemic.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Tony Sun, Yingpu Yu, Xianfang Wu, Ashley Acevedo, Ji-Dung Luo, Jiayi Wang, William M. Schneider, Brian Hurwitz, Brad R. Rosenberg, Hachung Chung, Charles M. Rice
Summary: Defective ADAR1 editing can lead to disorders, with the two protein isoforms p150 and p110 showing different contributions to RNA editing. The challenges in expressing p150 without p110 may explain the differences in editing landscape between the two isoforms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Di Lu, Jianxi Lu, Qiuli Liu, Qi Zhang
Summary: Stem cells play a critical role in organism development and tissue homeostasis. Recent studies have shown that RNA editing, mainly mediated by ADAR1, controls stem cell fate and function. ADAR1 is a multifunctional protein involved in embryonic development, cell differentiation, immune regulation, and gene editing technologies. This review summarizes the structure and function of ADAR1, with a focus on its role in stem cell self-renewal and differentiation. Targeting ADAR1 has emerged as a potential therapeutic strategy for both normal and dysregulated stem cells.
BIOMARKER RESEARCH
(2023)
Article
Oncology
Keiichiro Nakamura, Kunitoshi Shigeyasu, Kazuhiro Okamoto, Hirofumi Matsuoka, Hisashi Masuyama
Summary: This study aims to investigate the functional role and clinical significance of adenosine-to-inosine (A-to-I) RNA editing in endometrial cancer (EC). The results showed that ADAR1 expression was significantly associated with worse histology and lymph vascular space involvement in EC, while the level of AZIN1 RNA editing was also significantly associated with worse histology. ADAR1 expression was correlated with AZIN1 RNA editing level. Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients. Knockdown of ADAR1 led to increased expression of MDA-5, RIG-I, PKR, and IRF-7, which in turn resulted in increased levels of Bak and apoptosis in EC cells.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Ying Yang, Xiaoxiao Fan, Yun Ji, Ju Li, Zhaolai Dai, Zhenlong Wu
Summary: Glycine alleviates ER stress-induced apoptosis and dysfunction in intestinal barrier in a mTORC1-dependent manner. This study provides mechanistic insights into the protective effect of glycine on intestinal barrier integrity disrupted by ER stress.
Review
Cell Biology
Jizhe Liu, Fei Wang, Yindan Zhang, Jingfeng Liu, Bixing Zhao
Summary: RNA stability, RNA-protein interaction, and correct protein translation are significant forces in driving the transition from normal cell to malignant tumor. ADAR1 is an RNA editing enzyme that modifies the transcriptome by catalyzing the deamination of adenosine to inosine. Dysregulation of ADAR1 can lead to aberrant editing and affect phenotypic changes in cancer. ADAR1's overediting phenomenon is observed in many cancers and promotes tumor progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Xinfeng Guo, Silvia Liu, Yi Sheng, Mazen Zenati, Timothy Billiar, Alan Herbert, Qingde Wang
Summary: Variants of the RNA-editing enzyme ADAR1 cause inflammation in the brain, leading to Aicardi-Goutieres syndrome (AGS) due to innate immune activation. In this study, an AGS mouse model with the Adar P195A mutation was used to examine the RNA-editing status and innate immune activation. The mutation resulted in increased expression of interferon-stimulated genes (ISGs) in the brain, especially in the periventricular areas. Interestingly, this enhanced ISG expression was not associated with a decrease in overall RNA editing, suggesting that ADAR1 can regulate innate immune responses through Z-RNA binding.
Article
Psychiatry
Nicolas Salvetat, Fabrice Chimienti, Christopher Cayzac, Benjamin Dubuc, Francisco Checa-Robles, Pierrick Dupre, Sandie Mereuze, Vipul Patel, Catherine Genty, Jean-Philippe Lang, Jean-Francois Pujol, Philippe Courtet, Dinah Weissmann
Summary: The study found significant alterations in RNA editing of the PDE8A gene in the blood of patients with major depressive disorder and suicide attempters, suggesting a link to inflammation, cognition, and antidepressant treatment. Monitoring RNA editing in PDE8A in blood samples may help evaluate depressive state and suicide risk.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Turnee N. Malik, Erin E. Doherty, Vandana M. Gaded, Theodore M. Hill, Peter A. Beal, Ronald B. Emeson
Summary: ADAR-mediated RNA editing modulates various cellular pathways such as innate immunity and protein recoding and is considered as a strategy for treating genetic disorders. Research has shown that intracellular acidification increases RNA editing, mainly due to enhanced ADAR base-flipping and deamination rate under acidic pH conditions.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yusuke Shiromoto, Masayuki Sakurai, Moeko Minakuchi, Kentaro Ariyoshi, Kazuko Nishikura
Summary: The study shows that the nuclear isoform p110 of ADAR1 regulates R loop formation and genome stability at telomeres in cancer cells. Editing of A-C mismatches by ADAR1p110 assists in resolving telomeric R loops, crucial for the proliferation of telomerase-positive cancer cells. These findings highlight the pro-oncogenic nature of ADAR1p110 and identify ADAR1 as a promising therapeutic target for telomerase positive cancers.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Wei Huang, Yu-Meng Sun, Qi Pan, Ke Fang, Xiao-Tong Chen, Zhan-Cheng Zeng, Tian-Qi Chen, Shun-Xin Zhu, Li-Bin Huang, Xue-Qun Luo, Wen-Tao Wang, Yue-Qin Chen
Summary: This study identifies a novel snoRNA-related lncRNA, LNC-SNO49AB, with unique structures. The researchers found that LNC-SNO49AB is highly expressed in leukemia patients and its silencing dramatically suppresses leukemia progression. LNC-SNO49AB mainly localizes in the nucleolus and interacts with the nucleolar protein fibrillarin. It was also discovered that LNC-SNO49AB regulates genome-wide RNA A-to-I editing by enhancing ADAR1 dimerization, particularly affecting cell cycle pathways.
Article
Oncology
Shu-Yang Wang, Ling-Jie Zhang, Guo-Jun Chen, Qi-Qi Ni, Yuan Huang, Dan Zhang, Fang-Yi Han, Wen-Feng He, Li-Ling He, Yan-Qing Ding, Hong-Li Jiao, Ya-Ping Ye
Summary: RNA editing, specifically the COPA A-to-I editing event, is significantly increased in metastatic CRC tissues and associated with aggressive tumors. The COPA I164V protein activates ER stress and promotes CRC cell invasion and metastasis. Additionally, the COPA A-to-I editing rate is correlated with immune infiltration score.
Review
Cell Biology
Brian Song, Yusuke Shiromoto, Moeko Minakuchi, Kazuko Nishikura
Summary: ADAR1 catalyzes the conversion of adenosine to inosine in double-stranded RNA, affecting important biological processes within cells and playing roles in autoimmune diseases, cancer, and viral infections.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Review
Biology
Valentina Tassinari, Cristina Cerboni, Alessandra Soriani
Summary: ADAR1 mediates immune response modulation by A-to-I editing, preventing the development of autoimmune diseases and cancer. The activity of ADAR1 prevents the recognition of endogenous dsRNA by cellular sensors, avoiding excessive inflammation and IFN-I production.
Article
Medicine, Research & Experimental
Li Jiang, Yajing Hao, Changwei Shao, Qiulian Wu, Briana C. Prager, Ryan C. Gimple, Gabriele Sulli, Leo J. Y. Kim, Guoxin Zhang, Zhixin Qiu, Zhe Zhu, Xiang-Dong Fu, Jeremy N. Rich
Summary: This study reveals the role of A-to-I RNA editing mediated by ADAR1 in GBM stem cells and its potential as a therapeutic strategy. The elevated expression of ADAR1 and global RNA editomes in GSCs suggest their involvement in therapeutic resistance and relapse. Inhibition of ADAR1 or the upstream JAK/STAT pathway impairs GSC self-renewal and stemness. Additionally, the study highlights the critical role of RNA editing in ganglioside catabolism and its impact on GSCs.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Jingshan Tong, Xiao Tan, Xiangping Song, Man Gao, Denise Risnik, Suisui Hao, Kaylee Ermine, Peng Wang, Hua Li, Yi Huang, Jian Yu, Lin Zhang
Summary: This study found that CDK4/6 inhibitors promote immunogenic cell death of cancer cells by regulating the expression of p73 and DR5, enhancing the effects of chemotherapy and immune therapy.
Article
Oncology
Chaoyuan Kuang, Jingshan Tong, Kaylee Ermine, Manbo Cai, Fujun Dai, Suisui Hao, Francis Giles, Yi Huang, Jian Yu, Lin Zhang
Summary: The study demonstrates that NEO2734 more potently suppresses CRC cell growth than first generation BET inhibitors, inducing CRC cell apoptosis via both the intrinsic and extrinsic pathways. NEO2734 treatment simultaneously upregulates PUMA and DR5 to induce cell death, effectively suppressing CRC growth.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jingshan Tong, Xiao Tan, Suisui Hao, Kaylee Ermine, Xinyan Lu, Zhaojin Liu, Anupma Jha, Jian Yu, Lin Zhang
Summary: Targeting cyclin-dependent kinases (CDKs) has shown promising therapeutic potential against cancer. A recent study reveals that selective CDK4/6 inhibitors induce Death Receptor 5 (DR5) via p73, leading to increased sensitivity of colorectal cancer cells to therapy-induced apoptosis. This finding provides valuable insights into the anticancer mechanisms of CDKIs and their potential clinical applications in colorectal cancer.
Article
Multidisciplinary Sciences
Suisui Hao, Jingshan Tong, Anupma Jha, Denise Risnik, Darleny Lizardo, Xinyan Lu, Ajay Goel, Patricia L. Opresko, Jian Yu, Lin Zhang
Summary: Synthetic lethality can be used to target oncogenic drivers in cancer, and in this study, it was found that WRN helicase is required for the survival of MSI CRC cells. Depletion of WRN induces p53 and PUMA, leading to apoptosis in MSI CRC cells. The vulnerability of MSI CRCs to WRN loss is mediated by p53/PUMA-dependent apoptosis. WRN depletion or treatment with ML216 suppresses the growth of MSI CRCs in vitro and in vivo in a p53/PUMA-dependent manner.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Kaylee Ermine, Jian Yu, Lin Zhang
Summary: The RIP kinase family plays a crucial role in cell survival and cell death signaling. Dysregulation of RIP kinases is associated with various pathological conditions including inflammatory diseases, neurological diseases, and cancer. Alterations of RIP kinases in cancer cells contribute to tumor progression, therapeutic resistance, and escape from immune response. Targeting RIP kinases has potential implications for cancer treatment.
Article
Biochemistry & Molecular Biology
Brian J. Leibowitz, Guangyi Zhao, Wenxin Xia, Yuhan Wang, Hang Ruan, Lin Zhang, Jian Yu
Summary: In this study, the researchers discovered that mTOR inhibition can effectively suppress the formation of intestinal polyps, reverse established polyps, and prolong the lifespan of APC(Min/+) mice. Everolimus reduces the levels of p-4EBP1, p-S6, and Myc in the polyps and induces apoptosis of cells with activated beta-catenin. This cell death is accompanied by ER stress, activation of the extrinsic apoptotic pathway, innate immune cell recruitment, and subsequent T-cell infiltration.
Article
Oncology
Diala F. Hamade, Michael W. Epperly, Renee Fisher, Wen Hou, Donna Shields, Jan-Peter van Pijkeren, Amitava Mukherjee, Jian Yu, Brian J. Leibowitz, Anda M. Vlad, Lan Coffman, Hong Wang, M. Saiful Huq, Ziyu Huang, Claude J. Rogers, Joel S. Greenberger
Summary: Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Strategies to mitigate toxicity are important and LR-IFN-beta, a genetically engineered probiotic, shows potential as a safe and feasible radiation mitigator. LR-IFN-beta protects the intestine, improves survival, and can potentially revolutionize OC patient management when combined with platinum/taxane-based chemotherapy.
Review
Pharmacology & Pharmacy
Haris Saeed, Brian J. Leibowitz, Lin Zhang, Jian Yu
Summary: MYC is a proto-oncogene that plays a crucial role in the development of cancer cells. It is frequently rearranged and amplified in hematologic malignancies and is associated with cancer progression and therapeutic resistance. Activation of specific signaling pathways increases Myc levels, leading to stress adaptation, metabolic reprogramming, and immune evasion. Targeting Myc has proven challenging, but recent advances in understanding its mechanisms have opened up potential strategies for treatment, especially in colorectal cancer.
DRUG RESISTANCE UPDATES
(2023)
Meeting Abstract
Oncology
Kaylee Ermine, Dongshi Chen, Peng Wang, Jian Yu, Lin Zhang
Meeting Abstract
Oncology
Bogdan Kochetov, Phoenix D. Bell, Rebecca Raphael, Benjamin J. Raymond, Brian J. Leibowitz, Jingshan Tong, Brenda Diergaarde, Jian Yu, Reetesh K. Pai, Robert E. Schoen, Lin Zhang, Aatur Singhi, Shikhar Uttam.
Meeting Abstract
Oncology
Kaylee A. Ermine, Dongshi Chen, Peng Wang, Jian Yu, Lin Zhang
Article
Biochemistry & Molecular Biology
Hang Ruan, Brian J. Leibowitz, Yingpeng Peng, Lin Shen, Lujia Chen, Charlie Kuang, Robert E. Schoen, Xinghua Lu, Lin Zhang, Jian Yu
Summary: Mutant KRAS plays a crucial role in colorectal cancer by promoting Myc translation and Myc-dependent stress adaptation and proliferation. The combination of two FDA-approved drugs, Bortezomib and Everolimus, has been found to be highly effective against mutant KRAS colorectal cancer cells. This combination rapidly depletes Myc protein and induces cell death through various pathways. The study also shows that mutant KRAS colorectal cancer cells with elevated basal Myc and p-eIF2 alpha are more sensitive to the BR combination and exhibit characteristics of stress adaptation and cell death.
MOLECULAR BIOMEDICINE
(2022)
