Article
Multidisciplinary Sciences
Jiangbo Wei, Xianbin Yu, Lei Yang, Xuelian Liu, Boyang Gao, Boxian Huang, Xiaoyang Dou, Jun Liu, Zhongyu Zou, Xiao-Long Cui, Li-Sheng Zhang, Xingsen Zhao, Qinzhe Liu, P. Cody He, Caraline Sepich-Poore, Nicole Zhong, Wenqiang Liu, Yanhe Li, Xiaochen Kou, Yanhong Zhao, You Wu, Xuejun Cheng, Chuan Chen, Yiming An, Xueyang Dong, Huanyu Wang, Qiang Shu, Ziyang Hao, Tao Duan, Yu-Ying He, Xuekun Li, Shaorong Gao, Yawei Gao, Chuan He
Summary: This study reveals that FTO mediates m(6)A demethylation of LINE1 RNA in mouse embryonic stem cells, regulating LINE1 RNA abundance and the local chromatin state. It also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development.
Article
Chemistry, Medicinal
Sarah Huff, Indrasena Reddy Kummetha, Lingzhi Zhang, Lingling Wang, William Bray, Jiekai Yin, Vanessa Kelley, Yinsheng Wang, Tariq M. Rana
Summary: In this study, a new class of FTO inhibitors with high selectivity against m(6)A RNA demethylase and potent antiproliferative effects in different cancer models were developed through rational design and optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sarah Huff, Indrasena Reddy Kummetha, Lingzhi Zhang, Lingling Wang, William Bray, Jiekai Yin, Vanessa Kelley, Yinsheng Wang, Tariq M. Rana
Summary: Aberrant regulation of m(6)A RNA modification is implicated in the progression of multiple diseases, including cancer. A new class of FTO inhibitors derived from a previous lead FTO-04 has been designed with nanomolar potency and high selectivity against the homologous m(6)A RNA demethylase ALKBH5. These inhibitors show competitive activity against FTO and demonstrate potent antiproliferative effects in glioblastoma, acute myeloid leukemia, and gastric cancer models.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Xiaojie Gan, Zhihui Dai, Chunmei Ge, Haozan Yin, Yuefan Wang, Jian Tan, Shuhan Sun, Weiping Zhou, Shengxian Yuan, Fu Yang
Summary: This study elucidated the role of inflammation-related IL-17RA in the inflammation-carcinogenesis transformation of HCC through the analysis of m6A mRNA methylation. It was found that the decrease in m6A mRNA methylation might be associated with the development of HCC, and FTO was identified as the main modulator of m6A.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Yabing Nan, Shi Liu, Qingyu Luo, Xiaowei Wu, Pengfei Zhao, Wan Chang, Ruixiang Zhang, Yin Li, Zhihua Liu
Summary: The m6A modification of RNA plays an important role in esophageal squamous cell carcinoma (ESCC). The FTO-stabilized LINK-A promotes cell proliferation and chemoresistance in ESCC. Mechanistically, LINK-A enhances the interaction between MCM3 and CDK1, leading to increased MCM3 phosphorylation and facilitating cell-cycle progression and proliferation. LINK-A also disrupts the interaction between MCM3 and HIF-1a, promoting glycolysis and chemoresistance.
Review
Cell Biology
Mei Huang, Jianmin Guo, Lifei Liu, Haiming Jin, Xi Chen, Jun Zou
Summary: Osteoporosis is a common bone disease with unclear mechanisms. The m6A demethylase FTO plays an important role in regulating bone metabolism and osteoporosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Pei Cao, Yufan Wu, Ding Sun, Weigang Zhang, Junyi Qiu, Zuxiong Tang, Xiaofeng Xue, Lei Qin
Summary: This study suggests that m6A modification plays an important role in the progression of pancreatic carcinoma. IGF2BP2 is identified as a reliable marker and it modulates the stability of B3GNT6 mRNA, indicating that IGF2BP2 may serve as a potential prognostic marker and therapeutic target in the progression of pancreatic carcinoma.
Article
Agriculture, Dairy & Animal Science
Kan Li, Weichen Huang, Zhijun Wang, Qinghua Nie
Summary: This study revealed the negative association between m(6)A methylation and chicken adipogenesis. FTO was found to regulate CTNNB1 expression in a demethylation manner to promote lipogenesis in chicken preadipocytes.
JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY
(2022)
Article
Cell Biology
Weiyu Qiu, Yuexi Zhou, Haiwang Wu, Xiaoli Lv, Lilin Yang, Zhenxing Ren, He Tian, Qingying Yu, Jing Li, Weixian Lin, Ling Zhao, Songping Luo, Jie Gao
Summary: The study found that the downregulation of FTO in chorionic villi leads to disturbances in immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually causes SA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Shang Geng, Weiwei Zheng, Yan Zhao, Tianjun Xu
Summary: The study reveals that the m(6)A modification protein FTO promotes innate immunity and protects against viral infection in miiuy croaker. The m(6)A demethylase activity of FTO plays a crucial role in enhancing immunity. The FTO-mediated m(6)A modification in NOD1 mRNA activates the NOD-like receptor pathway, providing a molecular mechanism for immune regulation via RNA methylation in teleost.
Article
Cell Biology
Guanwen Zhou, Keqiang Yan, Jikai Liu, Lijian Gao, Xianzhou Jiang, Yidong Fan
Summary: This study found that the aberrant expression of FTO in bladder cancer is associated with poor prognosis. FTO overexpression promoted bladder cancer cell proliferation through the FTO/miR-576/CDK6 pathways. FTO could serve as a potential diagnostic or prognostic biomarker for bladder cancer.
CELL DEATH DISCOVERY
(2021)
Article
Cell Biology
Praveen K. Dubey, Mallikarjun Patil, Sarojini Singh, Shubham Dubey, Paras Ahuja, Suresh Kumar Verma, Prasanna Krishnamurthy
Summary: Endotoxemia-induced m6A methylation in the myocardium is associated with increased expression of inflammatory cytokine genes and reduced cardiac function, suggesting a potential role of m6A methylation in regulating myocardial inflammation and dysfunction during endotoxemia.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Oncology
Tadanobu Shimura, Raju Kandimalla, Yoshinaga Okugawa, Masaki Ohi, Yuji Toiyama, Chuan He, Ajay Goel
Summary: The study found that m(6)A regulators may serve as promising prognostic biomarkers in gastric cancer, with FTO being an important oncogene and a potential therapeutic target associated with EMT alterations in gastric cancer.
BRITISH JOURNAL OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Sarah Kassem Azzam, Habiba Alsafar, Abdulrahim A. Sajini
Summary: This article reviews the role of fat mass and obesity-associated protein (FTO) in obesity and cancer. Studies have shown that FTO can promote adipogenesis and tumorigenesis, and is associated with susceptibility to obesity and various cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Zhong-xin Jiang, Yi-ning Wang, Zi-yuan Li, Zhi-hui Dai, Yi He, Kun Chu, Jia-yi Gu, Yi-Xuan Ji, Ning-xia Sun, Fu Yang, Wen Li
Summary: The study demonstrates that m6A adenine regulates the function of GCs in female ovarian aging by modulating FTO demethylase, which in turn affects ovarian aging. FTO retards ovarian cell aging by regulating FOS expression.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Tao Tang, Ze-yu Yang, Di Wang, Xian-yan Yang, Jun Wang, Lin Li, Qian Wen, Lei Gao, Xiu-wu Bian, Shi-cang Yu
CELL AND BIOSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Shuyan Liu, Taishu Wang, Yulin Shi, Lu Bai, Shanshan Wang, Dong Guo, Yang Zhang, Yangfan Qi, Chaoqun Chen, Jinrui Zhang, Yingqiu Zhang, Quentin Liu, Qingkai Yang, Yang Wang, Han Liu
Summary: Liquid-liquid phase separation is a generic approach to studying the dynamic regulation of phase-separated assemblies and the roles of protein posttranslational modifications. USP42, a deubiquitylase, has been identified to play a pivotal role in nuclear speckle phase separation, mRNA splicing, and cancer cell growth. Inhibition of USP42 presents a novel anticancer strategy by targeting phase separation.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Gastroenterology & Hepatology
Shao-Lai Zhou, Chu-Bin Luo, Cheng-Li Song, Zheng-Jun Zhou, Hao-Yang Xin, Zhi-Qiang Hu, Rong-Qi Sun, Jia Fan, Jian Zhou
Summary: This study characterized the genomic evolution during ICC relapse and identified SLIT2 as a driver of tumor dissemination and tumor-associated neutrophil infiltration.
Article
Biology
Qiaoling Liu, Qi Xiao, Zhen Sun, Bo Wang, Lina Wang, Na Wang, Kai Wang, Chengli Song, Qingkai Yang
Summary: Targeting DNA repair pathway is an important therapeutic strategy for human cancers, but the failure of DNA repair inhibitors to benefit patients greatly necessitates the development of new strategies. This study reveals that EXOSC1 may act as an endogenous source of mutation in KIRC, promoting DNA damages and sensitizing cancer cells to DNA repair inhibitors, indicating that targeting EXOSC1 could be a potential therapeutic approach.
Article
Oncology
Jun Wang, Liang Yi, Qing-mei Kang, Ji Zhou, Tian-qing Chen, Jean-philippe Hugnot, Shi-cang Yu
Summary: Invasive growth along white matter tracts is a prominent clinicopathological feature of glioma and understanding the relevant clinical features and mechanisms is crucial for identifying new therapeutic targets and treatment strategies. Additionally, the correlation between glioma molecular typing, radiotherapy, TTFields, and glioma invasion along white matter tracts is also discussed.
Article
Oncology
Jiang-Jie Duan, Jiao Cai, Jun-jie Chen, Xiao-Xia Zheng, Tian-qing Chen, Xiao Zhang, Qing-Kai Yang, Shi-Cang Yu
Summary: Metastasis is the leading cause of death in colorectal cancer (CRC) patients. This study identified ALDH1A3 as a gene associated with CRC metastasis and poor prognosis. ALDH1A3 promotes invasion and metastasis by upregulating the expression of ZEB1 and SNAI2 through the inhibition of miR-200 family members. The ALDH1A3-specific inhibitor YD1701 attenuated CRC cell invasion in vitro and prolonged the survival of mice in xenograft models. Inhibiting ALDH1A3 with YD1701 could be an effective therapeutic approach to prevent CRC metastasis.
Article
Immunology
Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Qingkai Yang
Summary: Self-nonself discrimination is crucial for the immune system to respond to pathogens while maintaining tolerance. This study investigates how DNA sensors differentiate between self and nonself. The authors found that the DNA condenser spermine enhances cGAS activation and binding, specifically promoting condensation of viral DNA. Depletion of viral DNA-associated spermine reduces cGAS activation and impairs antiviral and anticancer immunity.
Article
Multidisciplinary Sciences
Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Caigang Liu, Qingkai Yang
Summary: The activation of cyclic GMP-AMP synthase (cGAS) is influenced by the mechanical flexibility of DNA, which is determined by DNA-sequence, damage, and length. Low dose radiation can induce cGAS-mediated acute immune surveillance (AIS) through repairable DNAs in a short period of time. This study establishes a direct connection between immunosurveillance and DNA mechanical features.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Xuejia Zhai, Ling Mao, Min Wu, Jie Liu, Shicang Yu
Summary: This article reviews the clinical research status, obstacles, advancements, and challenges of anti-MSLN CAR-T cell therapy, and summarizes strategies to improve its efficacy and safety. Anti-MSLN CAR-T cell therapy is a rapidly developing immunotherapy that has shown high safety but limited efficacy in clinical trials. Current approaches to enhance the proliferation and persistence of anti-MSLN CAR-T cells include local administration and the introduction of new modifications.
Article
Biochemistry & Molecular Biology
Shao-Lai Zhou, Zheng-Jun Zhou, Cheng-Li Song, Hao-Yang Xin, Zhi-Qiang Hu, Chu-Bin Luo, Yi-Jie Luo, Jia Li, Zhi Dai, Xin-Rong Yang, Ying-Hong Shi, Zheng Wang, Xiao-Wu Huang, Jia Fan, Jian Zhou
Summary: By conducting whole-genome sequencing on primary and early-recurrent HCC tumors, we identified two recurrence patterns and uncovered the evolutionary trajectories. We also identified recurrence-specific mutations and a potential therapeutic target for recurrent HCC. These findings provide important molecular insights for personalized therapy to improve patient survival.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)