Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Article
Biology
Lu Zhu, Qing Zhang, Ciro D. Cordeiro, Sudeep Banjade, Richa Sardana, Yuxin Mao, Scott D. Emr
Summary: The study reveals a novel ubiquitination modification implemented by Rsp5 adaptor proteins, which controls the recruitment and activity of Rsp5 to facilitate the turnover of membrane proteins.
Article
Biochemistry & Molecular Biology
Amanda B. Chai, Richard Callaghan, Ingrid C. Gelissen
Summary: The study demonstrates that NEDD4-1 regulates the expression and activity of P-gp, thereby facilitating the clearance of Aβ peptides from the brain. This finding offers a potential approach for the treatment of Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Cell Biology
Emanuela Senatore, Rosa Iannucci, Francesco Chiuso, Rossella Delle Donne, Laura Rinaldi, Antonio Feliciello
Summary: Primary cilia are microtubule-based sensory organelles that receive and transmit external signals to control cell growth, differentiation, and development. The formation and disassembly of primary cilia are finely regulated during the cell cycle. The ubiquitin-proteasome system and autophagy machinery play essential roles in cilia dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Physiology
Xinxin Lu, Haiqi Xu, Jiaqi Xu, Saien Lu, Shilong You, Xinyue Huang, Naijin Zhang, Lijun Zhang
Summary: This review summarizes the functions of NEDD4 family members in DNA damage response and discusses their roles in the cascade reactions induced by DNA damage.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Genetics & Heredity
James A. Conway, Grant Kinsman, Edgar R. Kramer
Summary: Parkinson's disease is a neurodegenerative disease with unclear molecular pathologies. Enhancing the clearance of alpha-synuclein, a proposed causative protein, is a central idea for PD research. NEDD4 ligases have been shown to influence the degradation of alpha-synuclein and may be potential therapeutic targets for PD. Understanding the expression and function of NEDD4 ligases in the brain is crucial for uncovering the mechanisms of PD.
Article
Biochemistry & Molecular Biology
Kai Li, Yi Niu, Yichuan Yuan, Jiliang Qiu, Yunxing Shi, Chengrui Zhong, Zhiyu Qiu, Keren Li, Zhu Lin, Zhenkun Huang, Chao Zhang, Dinglan Zuo, Wei He, Yunfei Yuan, Binkui Li
Summary: Insufficient thermal ablation can promote the progression of hepatocellular carcinoma (HCC) and upregulate the E3 ligase Nedd4. Nedd4 enhances the TGF-beta signal transduction, promoting tumor growth and metastasis. High Nedd4 expression correlates with aggressive tumor phenotypes and poor prognosis in HCC patients.
Article
Biology
Aiqin Sun, Jun Zhu, Song Xia, Yanling Li, Tiantian Wu, Genbao Shao, Wannian Yang, Qiong Lin
Summary: The study revealed that NEDD4 interacts with MEKK5 through a conserved WW3 domain, but MEKK5 is not a ubiquitination substrate of NEDD4 and instead negatively regulates NEDD4-mediated ubiquitination. Overexpression of MEKK5 significantly reduces NEDD4-promoted lung cancer cell migration.
Article
Biochemistry & Molecular Biology
Hao-Yu Chuang, Li-Yun Hsu, Chih-Ming Pan, Narpati Wesa Pikatan, Vijesh Kumar Yadav, Iat-Hang Fong, Chao-Hsuan Chen, Chi-Tai Yeh, Shao-Chih Chiu
Summary: The overexpression of NEDD4-1 in GBM and TMZ-resistant cells is associated with oncogenicity, tumorigenesis, and chemoresistance. Mechanistically, NEDD4-1 mediates the degradation of PTEN and upregulation of the AKT/NRF2/HO-1 signaling pathway, leading to increased defense against reactive oxygen species and higher resistance against TMZ treatment. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Liangzi Cao, Hao Li, Xiaofang Liu, Yubang Wang, Bowen Zheng, Chengzhong Xing, Naijin Zhang, Jingwei Liu
Summary: This study investigated the molecular alterations and clinical relevance of NEDD4 E3 ligase family genes in 33 cancer types. The findings revealed increased expression of NEDD4 members in pancreatic cancer and decreased expression in thyroid cancer. NEDD4 family genes exhibited a range of mutation frequencies, with HECW1 and HECW2 showing relatively high mutation rates. Breast cancer presented with a high frequency of NEDD4 copy number amplification. Additionally, NEDD4 family members were involved in various pathways such as p53, Akt, apoptosis, and autophagy, and their expression correlated with the survival of cancer patients.
Correction
Biochemistry & Molecular Biology
Daphne E. Lodes, Jiuhe Zhu, Nien-Pei Tsai
Summary: E3 ubiquitin ligase Nedd4-2 exerts neuroprotective effects during endoplasmic reticulum stress.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wenchun Fan, Katrina B. Mar, Levent Sari, Ilona K. Gaszek, Qiang Cheng, Bret M. Evers, John M. Shelton, Mary Wight-Carter, Daniel J. Siegwart, Milo M. Lin, John W. Schoggins
Summary: The research reveals that TRIM7 is a novel cell-intrinsic antiviral effector that restricts the spread of multiple human enteroviruses by targeting the viral 2BC protein for degradation. Selective pressure from TRIM7 led to the emergence of a TRIM7-resistant coxsackievirus with a mutation in the viral 2C ATPase/helicase.
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Correction
Oncology
Neng Wang, Qi Wang, Hailin Tang, Fengxue Zhang, Yifeng Zheng, Shengqi Wang, Jin Zhang, Zhiyu Wang, Xiaoming Xie
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yutian Zou, Shaoquan Zheng, Xinhua Xie, Feng Ye, Xiaoqian Hu, Zhi Tian, Shu-Mei Yan, Lu Yang, Yanan Kong, Yuhui Tang, Wenwen Tian, Jindong Xie, Xinpei Deng, Yan Zeng, Zhe-Sheng Chen, Hailin Tang, Xiaoming Xie
Summary: FGFR4 inhibition enhances sensitivity to anti-HER2 treatment in resistant breast cancer cells by triggering ferroptosis.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Fu Peng, Li Wang, Liang Xiong, Hailin Tang, Junrong Du, Cheng Peng
Summary: Breast cancer is the leading cause of death among women worldwide, and its incidence has sharply increased since 2008. Triple negative breast cancer (TNBC) is responsible for the majority of breast cancer-related deaths due to its aggressive growth and rapid metastasis. Maackiain (MA), a natural compound found in Chinese herbs, has been found to have anti-cancer effects in TNBC, suppressing cell proliferation, migration, and invasion. It also inhibits tumor growth and induces apoptosis through modulation of GADD45 alpha and miR-374a. These findings suggest the potential of MA as a drug candidate for TNBC therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Song Wu, Ruilin Pan, Jibu Lu, Xiaoling Wu, Jingdong Xie, Hailin Tang, Xing Li
Summary: In this study, we identified 15 ferroptosis-related genes associated with the prognosis of TNBC and developed a prognostic prediction model. The model showed satisfactory predictive ability and could potentially affect the prognosis of TNBC by regulating the tumor microenvironment.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Maryam Kohansal, Ali Ghanbarisad, Reza Tabrizi, Abdolreza Daraei, Mojtaba Kashfi, Hailin Tang, Cailu Song, Yongming Chen
Summary: tRNA-derived fragments (tRFs) have been identified as potential biomarkers for gastric cancer (GC). This study analyzed 10 articles investigating the clinical significance of tRFs in GC, and found that several tRFs were significantly upregulated or downregulated in GC compared to controls. The study also reviewed the functions of tRFs in gene expression regulation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Oncology
Xingyue Wang, Peng Li, Xiangxiang Jing, Yun Zhou, Yongfu Shao, Min Zheng, Junrui Wang, Haitao Ran, Hailin Tang
Summary: By constructing camouflaged nanoparticles PFH/ART@PLGA/Fe3O4-eFA, the challenges of poor water solubility of drugs in targeted therapy can be overcome. In vitro and in vivo experiments showed that the release of drugs induced by LIFU irradiation can suppress tumor growth through ROS generation and tumor cell ferroptosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Peng Liu, Zehao Wang, Xueqi Ou, Peng Wu, Yue Zhang, Song Wu, Xiangsheng Xiao, Yuehua Li, Feng Ye, Hailin Tang
Summary: Metastasis of breast cancer remains a major cause of cancer-related death globally. Recent research indicates that circRNAs are associated with tumorigenesis and metastasis in breast cancer. However, the biological mechanism of circRNAs in liver metastatic breast cancer is still unclear. In this study, we identified circEZH2 through microarray analysis and confirmed its existence and expression in liver metastases of breast cancer. We demonstrated that circEZH2 is upregulated in liver metastases and predicts poor prognosis in breast cancer patients. Functionally, circEZH2 promotes the vitality and invasion of breast cancer cells, and its knockdown has the opposite effects. Furthermore, circEZH2 overexpression promotes tumorigenesis and liver metastasis in vivo. Mechanistically, circEZH2 acts as a sponge for miR-217-5p, leading to upregulation of KLF5, which activates FUS transcription and facilitates the back-splicing program of circEZH2. Additionally, KLF5 transcriptionally upregulates CXCR4, thereby accelerating epithelial-mesenchymal transition in breast cancer. In conclusion, we have identified a novel feedback loop involving FUS/circEZH2/KLF5/CXCR4, and circEZH2 may serve as a potential biomarker and therapeutic target for breast cancer patients.
Review
Pharmacology & Pharmacy
Jianbo Zhou, Xiaofang Xie, Hailin Tang, Cheng Peng, Fu Peng
Summary: This article reviews the pharmacological attributes of sclareol and its potential applications in medicine, including anti-tumor, anti-inflammation, anti-pathogenic microbes, anti-diabetes and hypertension.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yutian Zou, Feng Ye, Yanan Kong, Xiaoqian Hu, Xinpei Deng, Jindong Xie, Cailu Song, Xueqi Ou, Song Wu, Linyu Wu, Yi Xie, Wenwen Tian, Yuhui Tang, Chau-Wei Wong, Zhe-Sheng Chen, Xinhua Xie, Hailin Tang
Summary: This study utilizes single-cell RNA sequencing to construct a high-resolution map of the tumor ecosystem in liver and brain metastases of breast cancer. The results show remarkable reprogramming of immunosuppressive cells in the metastatic ecosystem, as well as the negligible expression of PD-1 and PD-L1/2 in CD8+ T cells and cancer/immune/stromal cells. The interactions between LAG3-LGALS3 and TIGIT-NECTIN2 are found to play dominant roles in immune escape.
Article
Pharmacology & Pharmacy
Zhengyuan Yu, Hailin Tang, Shaomu Chen, Yufeng Xie, Liyan Shi, Shuhua Xia, Min Jiang, Jiaoyang Li, Dongqin Chen
Summary: This study explores the role of the long non-coding RNA (lncRNA) LOC85009 in docetaxel (DTX) resistance of lung adenocarcinoma (LUAD) and reveals its potential as a target for reversing DTX resistance. The findings demonstrate that LOC85009 is lowly expressed in DTX-resistant LUAD cells and that its overexpression inhibits DTX resistance, cell proliferation, and triggers apoptosis. Furthermore, it is discovered that LOC85009 is transferred from LUAD cells to DTX-resistant LUAD cells via exosomes, where it inhibits DTX resistance, proliferation, autophagy, and induces apoptosis.
DRUG RESISTANCE UPDATES
(2023)
Article
Cell Biology
Yan Zeng, Wei Du, Zhongying Huang, Song Wu, Xueqi Ou, Jinhui Zhang, Cheng Peng, Xiaoqing Sun, Hailin Tang
Summary: Breast cancer is the most common cancer worldwide and is the leading cause of female mortality. Recent studies have shown that circRNAs are associated with the progression of breast cancer. Exploring circRNAs could lead to the development of targeted therapies for breast cancer liver metastasis and improving patient outcomes.
CELL DEATH DISCOVERY
(2023)
Article
Medicine, Research & Experimental
Aiqun Liu, Baohong Jiang, Cailu Song, Qizhi Zhong, Yufan Mo, Ruiqin Yang, Ciyu Chen, Cheng Peng, Fu Peng, Hailin Tang
Summary: In this study, it was found that isoliquiritigenin (ISL) inhibits the expression of circ0030018, which plays a critical role in the growth and invasion of glioma. Silencing circ0030018 significantly reduces glioma growth and invasion, and enhances oxidative stress in glioma cells. Mechanistic studies revealed that circ0030018 functions through the miR-1236/HER2 signaling pathway. These findings suggest that circ0030018 could serve as a potential biomarker or therapeutic target for glioma.
Article
Pharmacology & Pharmacy
Zhi Jiang, Qiuping Zou, Qicheng Chen, Junhong Zhang, Hailin Tang, Jingbao Chen, You Qin, Liming Yang, Zhiqiang Chen, Lixing Cao
Summary: This study investigated the mechanism and pharmacological effect of Wuda Granule (WDG) on gastrointestinal motility disorder (GMD) through network analysis, animal experiments, and clinical trials. The results showed that WDG improved GMD by inhibiting inflammation and promoting gastrointestinal motility, providing new insights and references for future research and clinical treatment of GMD.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Immunology
Xiao Zhang, Pengpeng Zhang, Ansheng Cong, Yanlong Feng, Hao Chi, Zhijia Xia, Hailin Tang
Summary: This review explores the complex molecular networks of thymic epithelial tumors (TETs), focusing on key aspects such as chromosomal abnormalities, gene mutations and expressions, gene rearrangements, and epigenetic changes. It also examines the influence of the tumor microenvironment on TET behavior and therapeutic responses. A thorough understanding of these features can enhance diagnostic accuracy, refine prognostic assessments, and tailor targeted therapeutic strategies for TETs.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Genetics & Heredity
Abdolmajid Ghasemian, Hadeel A. Omear, Yaser Mansoori, Pardis Mansouri, Xinpei Deng, Farzaneh Darbeheshti, Elham Zarenezhad, Maryam Kohansal, Babak Pezeshki, Zhangling Wang, Hailin Tang
Summary: Colorectal cancer is a fatal cancer, and lncRNAs play regulatory roles in cell proliferation and immune responses via the JAK/STAT signaling pathway, making them potential biomarkers and therapeutic targets.
FRONTIERS IN GENETICS
(2023)