Article
Biotechnology & Applied Microbiology
Guowei Li, Xiufang Lu, Qianqian Xu, Yanping Jin
Summary: To investigate the role of FDX1 methylation in glioma, we used bioinformatic analysis and experimental models to demonstrate the regulatory mechanism. Our findings showed that C-MYC upregulates FDX1 through YTHDF1, inhibiting mitophagy in glioma cells. Functional experiments revealed that C-MYC also enhances glioma cell proliferation and invasion via the YTHDF1-FDX1 pathway. In vivo experiments demonstrated the high sensitivity of glioma cells to cuproptosis. Overall, our study suggests that C-MYC promotes the malignant phenotype of glioma cells by upregulating FDX1 through m6A methylation.
Article
Oncology
Jinpeng Hu, Guoqing Zhang, Yongfeng Wang, Kai Xu, Lian Chen, Gang Luo, Jinkun Xu, Hao Li, Dongmei Pei, Xiang Zhao, Zhengting Guo, Xinqiao Li, Shengliang Zong, Yang Jiang, Zhitao Jing
Summary: This study identifies a novel circular RNA, circGNB1, which is upregulated in glioma and closely associated with poor prognosis. Functional assays reveal that circGNB1 overexpression promotes the viability, proliferation, invasion, and neurosphere formation of glioma stem cells. Mechanistically, circGNB1 upregulates the expression of oncogene XPR1 by sponging miR-515-5p and miR-582-3p. XPR1, in turn, promotes the malignant phenotype of glioma stem cells through upregulating IL6 expression and activating JAK2/STAT3 signaling. Additionally, the RNA binding protein IGF2BP3 binds to and stabilizes circGNB1, thus enhancing its effects on glioma stem cells. This study uncovers the crucial role of circGNB1 in tumorigenesis and malignant progression of glioma, providing a promising cancer biomarker.
CANCER CELL INTERNATIONAL
(2023)
Article
Medicine, Research & Experimental
Joo-Hui Han, Hyun-Soo Park, Do-Hyung Lee, Jun-Hwan Jo, Kyung-Sun Heo, Chang-Seon Myung
Summary: The study suggests that PDGF-BB-induced VSMC autophagy is mainly regulated by Erk1/2, independent of the mTOR pathway. Targeting autophagy modulation may be a potential therapeutic strategy for addressing abnormal VSMC proliferation and migration.
Article
Gastroenterology & Hepatology
Alessandra Gentilini, Giulia Lori, Alessandra Caligiuri, Chiara Raggi, Giovanni Di Maira, Mirella Pastore, Benedetta Piombanti, Tiziano Lottini, Annarosa Arcangeli, Stefania Madiai, Nadia Navari, Jesus M. Banales, Sabina Di Matteo, Domenico Alvaro, Lea Duwe, Jesper B. Andersen, Alessandro Tubita, Ignazia Tusa, Luca Di Tommaso, Claudia Campani, Elisabetta Rovida, Fabio Marra
Summary: This study revealed the important role of ERK5 in the growth and migration of CCA cells, as well as its involvement in the protumorigenic crosstalk between the tumor and the microenvironment.
Article
Cell Biology
Jinkun Xu, Guoqing Zhang, Jinpeng Hu, Hao Li, Junshuang Zhao, Shengliang Zong, Zhengting Guo, Yang Jiang, Zhitao Jing
Summary: This study identified a novel up-regulated circular RNA, circRPPH1, in Glioma stem cells (GSCs), which was associated with poor survival. circRPPH1 promoted the malignant phenotype and self-renewal ability of GSCs. Mechanistically, UPF1 interacted with circRPPH1 to maintain its stability, leading to enhanced interaction between circRPPH1 and transcription factor ATF3 and further transcription of UPF1 and Nestin. This formed a feedback loop resulting in continuous enhancement of tumorigenicity in GSCs through increased Nestin expression. Additionally, ATF3 activated the TGF-beta signaling pathway to drive GSCs tumorigenesis. Knocking down circRPPH1 expression inhibited proliferation and clonogenicity of GSCs, while overexpression of circRPPH1 enhanced self-renewal of GSCs. These findings suggest that the UPF1/circRPPH1/ATF3 pathway maintains the self-renewal ability of GSCs by interacting with RNA-binding protein and activating the TGF-beta signal pathway. Breaking this feedback loop could serve as a novel therapeutic target in GBM treatment.
CELL DEATH & DISEASE
(2022)
Article
Genetics & Heredity
Quanwei Zhou, Min Wei, Wenyue Shen, Sheng Huang, Jianfeng Fan, He Huang
Summary: This study found that SYK is significantly upregulated in diffuse glioma and is associated with malignant phenotypes and poor prognosis. Functional enrichment and immune infiltration analyses showed that SYK is involved in shaping the immunosuppressive microenvironment. Additionally, SYK expression is closely associated with immune checkpoint molecules and M2 macrophage infiltration. Based on these findings, SYK may serve as a potential prognosis biomarker and immunotherapeutic target for diffuse glioma.
FRONTIERS IN GENETICS
(2022)
Article
Neurosciences
Jinfang Xu, Jianli Wang, Mingfei Zhao, Chenguang Li, Shen Hong, Jianmin Zhang
Summary: This study investigates the regulation of the lncRNA/miRNA axis on KNG1 in glioma. The results show that LINC01018 sponges miR-942-5p to regulate the expression of KNG1, which is associated with the survival rate of patients. MiR-942-5p is highly expressed, while KNG1 is lowly expressed in glioma, and they have a negative correlation. Knockdown of LINC01018 or KNG1 and miR-942-5p mimic enhance the migration, invasion, and proliferation of glioma cells, and regulate the expressions of metastasis-related and proliferation-related genes. LINC01018 knockdown and miR-942-5p mimic promote glioma tumor growth in mice. The LINC01018/miR-942-5p/KNG1 pathway plays a regulatory role in the development of glioma cells in vitro and in vivo.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Mantao Chen, Luyuan Zhang, Renya Zhan, Xiujue Zheng
Summary: In this study, we investigated the role and mechanism of action of a novel HDAC inhibitor, pracinostat, in human glioma. Our results demonstrated that pracinostat inhibited cell proliferation, induced apoptosis, and suppressed cell migration and invasion. These effects were achieved through modulation of specific signaling pathways.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Oncology
Yunfei Liao, Zaili Luo, Yaqi Deng, Feng Zhang, Rohit Rao, Jiajia Wang, Lingli Xu, Shiva Senthil Kumar, Satarupa Sengupta, Mariko DeWire-Schottmiller, Kalen Berry, Matthew Garrett, Maryam Fouladi, Rachid Drissi, Qing Richard Lu
Summary: DIPG cells exhibit phenotypic heterogeneity and OLIG2 is dispensable for the growth of certain DIPG cells, while regulating the phenotype and tumor growth of other DIPG cells expressing OLIG2. Downregulation of OLIG2 leads to deregulation of adaptive YAP1 and EGFR signaling, and targeting these pathways inhibits the growth of OLIG2-deficient DIPG cells, suggesting therapeutic potential in treating DIPG tumors with low OLIG2 expression.
Article
Cell Biology
Sinthu Pathmanapan, Raymond Poon, Tomasa Barrientos De Renshaw, Puviindran Nadesan, Makoto Nakagawa, Gireesh A. Seesankar, Adrian Kwan Ho Loe, Hongyuan H. Zhang, Joan J. Guinovart, Jordi Duran, Christopher B. Newgard, Jay S. Wunder, Benjamin A. Alman
Summary: Chondrosarcomas, the most common malignancy of cartilage, are linked to genetic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes. The presence of IDH mutations in enchondromas, the benign precursor lesions, suggests that these mutations occur early in the development of malignancy. Our studies on mutant IDH chondrosarcomas and mutant Idh mice have found that glycogen is deposited exclusively in mutant cells, and its utilization influences tumor cell behavior and energy pathways. The interaction between mutant IDH1 and hypoxia-inducible factor 1a (HIF1a) appears to regulate key enzymes in glycogen metabolism, suggesting a critical role for glycogen in enchondromas and chondrosarcomas.
Article
Pathology
Wei Ji, Jiantong Jia, Chao Cheng, Yong Xiao, Junfei Shao, Hongyi Liu
Summary: The study revealed that LINC00662 is highly expressed in glioma and associated with malignant phenotype. Knockdown of LINC00662 inhibits glioma proliferation and invasion, suggesting a potential therapeutic strategy. LINC00662 regulates the expression of STAT3 through ceRNA mechanism with miR-340-5p.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Oncology
Zihang Chen, Huizhi Wang, Zongpu Zhang, Jianye Xu, Yanhua Qi, Hao Xue, Zijie Gao, Rongrong Zhao, Shaobo Wang, Shouji Zhang, Wei Qiu, Xing Guo, Gang Li
Summary: Surface expression of glucose-regulated protein 78 (csGRP78) was found to be preferentially expressed in MES GSCs, and targeting csGRP78 effectively suppressed self-renewal and radioresistance of MES GSCs both in vitro and in vivo by downregulating STAT3, NF-kappa B, and C/EBP beta pathways, potentially through regulation of downstream molecule BACE2. These findings suggest that blocking csGRP78 with a high-specificity antibody could be a promising therapeutic strategy for glioblastoma treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jay Kataria, Jack Kerr, Sandra R. Lourenssen, Michael G. Blennerhassett
Summary: Recent studies have shown that the tyrosine kinase inhibitor nintedanib (NIN) can inhibit hyperplasia of intestinal smooth muscle cells (ISMC) in Crohn's disease (CD) and similar pathologies, reducing the expression of inflammatory cytokines.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Sabbir Khan, Rajasekaran Mahalingam, Shayak Sen, Emmanuel Martinez-Ledesma, Arshad Khan, Kaitlin Gandy, Frederick F. Lang, Erik P. Sulman, Kristin D. Alfaro-Munoz, Nazanin K. Majd, Veerakumar Balasubramaniyan, John F. de Groot
Summary: Interferon signaling plays a crucial role in glioma tumorigenesis, with high IFN/STAT1 signaling associated with poor survival outcomes and mesenchymal phenotype in patients. Targeting IFN signaling may be beneficial for a specific subgroup of GBM patients, with IFN-beta showing promise as a potential adjuvant therapy.
Article
Biochemistry & Molecular Biology
Yi Wu, Yanjie Hao, Qing'xin Zhuang, Xiaoli Ma, Chao Shi
Summary: This study found that M2 macrophage polarization is the main immune infiltration pattern in gastric cancer, and low expression of AKR1B10 induces M2 macrophage polarization and promotes the malignant transformation of gastric cancer.
BIOSCIENCE REPORTS
(2023)
Article
Cell & Tissue Engineering
Qinjie Weng, Jincheng Wang, Jiajia Wang, Danyang He, Zuolin Cheng, Feng Zhang, Ravinder Verma, Lingli Xu, Xinran Dong, Yunfei Liao, Xuelian He, Andrew Potter, Liguo Zhang, Chuntao Zhao, Mei Xin, Qian Zhou, Bruce J. Aronow, Perry J. Blackshear, Jeremy N. Rich, Qiaojun He, Wenhao Zhou, Mario L. Suva, Ronald R. Waclaw, S. Steven Potter, Guoqiang Yu, Q. Richard Lu
Article
Neurosciences
Linda L. Boshans, Daniel C. Factor, Vijender Singh, Jia Liu, Chuntao Zhao, Ion Mandoiu, Q. Richard Lu, Patrizia Casaccia, Paul J. Tesar, Akiko Nishiyama
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Multidisciplinary Sciences
Jiajia Wang, Lijun Yang, Chen Dong, Jincheng Wang, Lingli Xu, Yueping Qiu, Qinjie Weng, Chuntao Zhao, Mei Xin, Q. Richard Lu
Article
Multidisciplinary Sciences
Cuiqing Fan, Chuntao Zhao, Feng Zhang, Meenu Kesarwani, Zhaowei Tu, Xiongwei Cai, Ashley Kuenzi Davis, Lingli Xu, Cindy L. Hochstetler, Xiaoyi Chen, Fukun Guo, Gang Huang, Mohammad Azam, Weidong Tian, Q. Richard Lu, Yi Zheng
Summary: The loss of mTOR in hematopoietic stem cells leads to increased proliferation and chromatin accessibility, activating global gene expression. This adaptation is driven by rewiring and activation of the ERK/MNK/eIF4E signaling pathway, which enhances protein translation and promotes increased c-Myc gene expression. This adaptive mechanism allows stem cells and potentially leukemia cells to thrive despite mTOR inhibition, offering insight into evasive resistance mechanisms to mTOR-targeted therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Hematology
Zhaowei Tu, Chen Wang, Ashley K. Davis, Mengwen Hu, Chuntao Zhao, Mei Xin, Q. Richard Lu, Yi Zheng
Summary: The Chd8 gene encodes a chromatin remodeler essential for normal hematopoiesis, with its deficiency leading to severe anemia and instability of HSPCs. CHD8 maintains hematopoiesis by regulating ATM-P53-mediated survival of HSPCs.
Article
Immunology
Dianyu Chen, Yan Wang, Godhev K. Manakkat Vijay, Shujie Fu, Colt W. Nash, Di Xu, Danyang He, Nathan Salomonis, Harinder Singh, Heping Xu
Summary: Through single-cell transcriptomic analyses, researchers found that GC B cells with higher-affinity mutations had increased expression of OXPHOS genes. Deletion of mitochondrial genes in GC B cells resulted in reduced cell division and impaired positive selection. Enhancement of OXPHOS activity promoted affinity maturation in GC B cells.
Article
Immunology
Danyang He, Heping Xu, Huiyuan Zhang, Ruihan Tang, Yangning Lan, Ruxiao Xing, Shaomin Li, Elena Christian, Yu Hou, Paul Lorello, Barbara Caldarone, Jiarui Ding, Lan Nguyen, Danielle Dionne, Pratiksha Thakore, Alexandra Schnell, Jun R. Huh, Orit Rozenblatt-Rosen, Aviv Regev, Vijay K. Kuchroo
Summary: This study reveals that cellular metabolism regulates microglial function during neurodevelopment. The IL-33 signaling axis, coupled with AKT activity, promotes mitochondrial metabolism and phagocytic function in microglia. This microglia-astrocyte circuit plays a crucial role in the metabolic adaptation and phagocytic function of microglia during early development.
Article
Immunology
Yan Wang, Dianyu Chen, Di Xu, Chao Huang, Ruxiao Xing, Danyang He, Heping Xu
Summary: The meninges are identified as a distinct reservoir for B cell development, continuously supplying developing B cells through a circulation-independent route and implementing in situ negative selection to ensure a locally non-self reactive immune repertoire.
Article
Cell Biology
Sharon M. Louie, Aaron L. Moye, Irene G. Wong, Emery Lu, Andrea Shehaj, Carolina Garcia-de-Alba, Erhan Ararat, Benjamin A. Raby, Bao Lu, Margherita Paschini, Roderick T. Bronson, Carla F. Kim
Summary: This research demonstrates the progenitor cell functions of lung epithelial organoid cells after reintroduction to the lung, and reveals methods to investigate the potential of lung progenitor cells and model transitional cell states relevant to pathogenic features of lung disease in vivo.
Article
Immunology
Ruihan Tang, Nandini Acharya, Ayshwarya Subramanian, Vinee Purohit, Marcin Tabaka, Yu Hou, Danyang He, Karen O. Dixon, Connor Lambden, Junrong Xia, Orit Rozenblatt-Rosen, Raymond A. Sobel, Chao Wang, Aviv Regev, Ana C. Anderson, Vijay K. Kuchroo
Summary: Dendritic cells (DCs) play a crucial role in modulating the immune response by sensing environmental cues. This study identifies Bat3 as an endogenous regulator of DC function, showing that loss of Bat3 expression alters the T cell compartment, resulting in the attenuation of autoimmunity and acceleration of tumor growth.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Ravinder Verma, Xiameng Chen, Dazhuan Xin, Zaili Luo, Sean Ogurek, Mei Xin, Rohit Rao, Kalen Berry, Richard Lu
Summary: Intermediate progenitor cells play a crucial role in the development of malignant gliomas.
Article
Oncology
Khalid W. Kalim, Jun-Qi Yang, Mark Wunderlich, Vishnu Modur, Phuong Nguyen, Yuan Li, Ting Wen, Ashley Kuenzi Davis, Ravinder Verma, Qing Richard Lu, Anil G. Jegga, Yi Zheng, Fukun Guo
Summary: Targeting Cdc42 in Treg cells has shown promising therapeutic potential in cancer immunotherapy, by enhancing antitumor T-cell immunity without triggering autoimmune reactions. This approach involves inducing Treg cell instability through Cdc42 targeting, leading to improved immune responses against tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Letter
Biochemistry & Molecular Biology
Erhan Ararat, Sharon M. Louie, Emery Lu, Margherita Paschini, David M. Raiser, Carla F. Kim
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Meeting Abstract
Oncology
Rohit Rao, Ravinder Verma, Jincheng Wang, Qing Richard Lu