Article
Oncology
Yi Yang, Siqi Wang, Jiaoyang Cai, Jianwei Liang, Yingwen Zhang, Yangyang Xie, Fei Luo, Jingyan Tang, Yijin Gao, Shuhong Shen, Haizhong Feng, Yanxin Li
Summary: This study provides insights into the mechanism by which ARHGEF12 regulates the malignancy of neuroblastoma and suggests a potential therapeutic approach by targeting ARHGEF12 with a small molecule inhibitor.
Article
Oncology
Qiqi Shi, Bo Yu, Yingwen Zhang, Yi Yang, Chenxin Xu, Mingda Zhang, Guoyu Chen, Fei Luo, Bowen Sun, Ru Yang, Yanxin Li, Haizhong Feng
Summary: TRIM24 is overexpressed in neuroblastoma and is associated with poor prognosis. Knockout of TRIM24 promotes cell differentiation, reduces stemness, and inhibits tumor growth. In addition, TRIM24 knockout activates the retinoic acid pathway. Therefore, TRIM24 may be a critical target in neuroblastoma differentiation therapy.
Article
Oncology
Zhiwei Dong, Kok Siong Yeo, Gonzalo Lopez, Cheng Zhang, Erin N. Dankert Eggum, Jo Lynne Rokita, Choong Yong Ung, Taylor M. Levee, Zuag Paj Her, Cassie J. Howe, Xiaonan Hou, Janine H. van Ree, Shuai Li, Shuning He, Ting Tao, Karen Fritchie, Jorge Torres-Mora, Julia S. Lehman, Alexander Meves, Gina L. Razidlo, Komal S. Rathi, S. John Weroha, A. Thomas Look, Jan M. van Deursen, Hu Li, Jennifer J. Westendorf, John M. Maris, Shizhen Zhu
Summary: Research has shown that GAS7 gene is preferentially deleted in high-risk MYCN-driven neuroblastoma, and its deficiency accelerates metastasis in neuroblastoma models. Loss of GAS7 affects cell-cell interaction and contact among tumor cells, identifying a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma.
Article
Biochemistry & Molecular Biology
Xiaosong Hu, Ruochen Liu, Jianbing Hou, Wen Peng, Sicheng Wan, Minghao Xu, Yongsen Li, Guanghui Zhang, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: This study reveals the critical oncogenic role of SMARCE1 gene in neuroblastoma, particularly in cases with MYCN amplification. SMARCE1 interacts with MYCN to mediate transcriptional activation of downstream target genes, promoting neuroblastoma proliferation and tumorigenicity. These findings provide a new potential therapeutic target for neuroblastoma with 17q21-ter gain and MYCN amplification.
Article
Cell Biology
Xiaoling Zhang, Xianling Cong, Xiangting Jin, Yu'e Liu, Tong Zhang, Xinyuan Fan, Xiyao Shi, Xiaoying Zhang, Xue Wang, Yong-Guang Yang, Xiangpeng Dai
Summary: The transcription factor MYCN is frequently amplified and overexpressed in various cancers, and is considered undruggable. In this study, BRCA1-associated protein-1 (BAP1) is identified as an upstream regulator that stabilizes MYCN through direct binding. Depletion of BAP1 inhibits neuroblastoma tumor cell growth and migration, and confers cellular resistance to BET protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Our findings suggest that BAP1 could be a potential therapeutic target for MYCN-amplified neuroblastoma.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Anders Valind, Bronte Manouk Verhoeven, Jens Enoksson, Jenny Karlsson, Gustav Christensson, Adriana Manas, Kristina Aaltonen, Caroline Jansson, Daniel Bexell, Ninib Baryawno, David Gisselsson, Catharina Hagerling
Summary: Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. Novel therapeutic alternatives that target the immune microenvironment can effectively inhibit the relapse of MNA(+) neuroblastoma.
Article
Biochemistry & Molecular Biology
Belamy B. Cheung, Ane Kleynhans, Rituparna Mittra, Patrick Y. Kim, Jessica K. Holien, Zsuzsanna Nagy, Olivia C. Ciampa, Janith A. Seneviratne, Chelsea Mayoh, Mukesh Raipuria, Satyanarayana Gadde, Hassina Massudi, Iris Poh Ling Wong, Owen Tan, Andrew Gong, Aldwin Suryano, Sonya M. Diakiw, Bing Liu, Greg M. Arndt, Tao Liu, Naresh Kumar, Olle Sangfelt, Shizhen Zhu, Murray D. Norris, Michelle Haber, Daniel R. Carter, Michael W. Parker, Glenn M. Marshall
Summary: A new small molecule compound, SE486-11, was identified to synergistically enhance the cytotoxic effects of HDAC inhibitor SAHA in MYCN-driven neuroblastoma. The combination of SAHA and SE486-11 decreased MYCN expression, inhibited tumor growth, and disrupted a positive feedback loop between MYCN and USP5, suggesting a potential therapeutic approach for MYCN-driven neuroblastoma.
Article
Cell Biology
Yajie Yu, Jane Ding, Shunqin Zhu, Ahmet Alptekin, Zheng Dong, Chunhong Yan, Yunhong Zha, Han-Fei Ding
Summary: Metabolic reprogramming driven by oncogenes like MYC is closely related to growth promotion, but also leads to potential therapeutic metabolic dependencies; MYCN-amplified neuroblastoma promotes pyrimidine nucleotide production by upregulating DHODH and other enzymes, and inhibition of DHODH can effectively suppress proliferation and tumorigenicity of these cancer cells.
CELL DEATH & DISEASE
(2021)
Review
Cell Biology
Xiyao Shi, Ying Wang, Longhui Zhang, Wenjie Zhao, Xiangpeng Dai, Yong-Guang Yang, Xiaoling Zhang
Summary: Bromodomain and extra-terminal domain (BET) family proteins are crucial for regulating cancer development and have therapeutic potential in various cancers. Blocking BET proteins is a commonly used strategy to treat high-risk neuroblastoma with MYCN amplification. This article summarizes the functions of BET proteins as epigenetic readers and the therapeutic potential of BET/BRD4 inhibitors in neuroblastoma, as well as discusses combined therapeutic strategies for BET inhibitor-resistant neuroblastoma.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Silvia Lampis, Salvatore Raieli, Luca Montemurro, Damiano Bartolucci, Camilla Amadesi, Sonia Bortolotti, Silvia Angelucci, Anna Lisa Scardovi, Giammario Nieddu, Lucia Cerisoli, Francesca Paganelli, Sabrina Valente, Matthias Fischer, Alberto Maria Martelli, Gianandrea Pasquinelli, Andrea Pession, Patrizia Hrelia, Roberto Tonelli
Summary: This study found that the combination of MYCN-specific antigene oligonucleotide BGA002 and retinoic acid (RA) can restore sensitivity to RA in MYCN-amplified neuroblastoma (MNA-NB) patients and improve their survival rate. Furthermore, by targeting MYCN, a cancer-specific inhibition of the mTOR pathway occurs only in MNA-NB, avoiding the side effects of targeting mTOR in normal cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Ling Tao, Myrthala Moreno-Smith, Rodrigo Ibarra-Garcia-Padilla, Giorgio Milazzo, Nathan A. Drolet, Blanca E. Hernandez, Young S. Oh, Ivanshi Patel, Jean J. Kim, Barry Zorman, Tajhal Patel, Abu Hena Mostafa Kamal, Yanling Zhao, John Hicks, Sanjeev A. Vasudevan, Nagireddy Putluri, Cristian Coarfa, Pavel Sumazin, Giovanni Perini, Ronald J. Parchem, Rosa A. Uribe, Eveline Barbieri
Summary: This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation, and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression.
Article
Oncology
Marialena Pouliou, Marianna A. Koutsi, Lydia Champezou, Angeliki-Ioanna Giannopoulou, Giannis Vatsellas, Christina Piperi, Marios Agelopoulos
Summary: This study assesses the upregulation of metabolism-related transcription factors (TFs) in neuroblastoma cells due to the amplification of MYCN. The results reveal the regulatory mechanism of MYCN in the metabolic processes of neuroblastoma.
Article
Oncology
Weiming Chen, Xiwei Hao, Binyi Yang, Yuezhen Zhang, Lingyun Sun, Yanan Hua, Li Yang, Jiabin Yu, Jing Zhao, Lin Hou, Hongting Lu
Summary: The study showed that miR-17-5p derived from MYCN-amplified NB cell exosomes promoted the migration and proliferation of non-MYCN amplified cells, indicating a malignant role for miR-17-5p in exosomes.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Chemistry, Medicinal
Honoka Obata, Atsushi B. Tsuji, Hitomi Sudo, Aya Sugyo, Kaori Hashiya, Hayato Ikeda, Masatoshi Itoh, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Toshikazu Bando, Hiroshi Sugiyama, Ming-Rong Zhang
Summary: Auger electrons can efficiently damage specific DNA sites that play a key role in cancer cell survival. This study developed a Pt-191-labeled agent targeting the oncogene MYCN and demonstrated its ability to efficiently bind to DNA, cause DNA damage, and decrease MYCN gene expression and cell viability. However, the delivery of the agent to tumors needs improvement.
Article
Biochemistry & Molecular Biology
Xianbing Zhang, Xinyi Guo, Ran Zhuo, Yanfang Tao, Wenxia Liang, Randong Yang, Yanling Chen, Haibo Cao, Siqi Jia, Juanjuan Yu, Xinmei Liao, Xiaolu Li, Fang Fang, Gen Li, Di Wu, Yunyun Xu, Zhiheng Li, Jian Pan, Jian Wang
Summary: The study found that MZ1 inhibited the proliferation of neuroblastoma cells, increased cell apoptosis, and demonstrated significant therapeutic effects in experimental animals. The mechanism may involve the suppression of N-Myc and C-Myc expression as well as the MAPK signaling pathway. These findings suggest the potential of MZ1 as a therapeutic approach for neuroblastoma treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)