Review
Oncology
Damiano Bartolucci, Luca Montemurro, Salvatore Raieli, Silvia Lampis, Andrea Pession, Patrizia Hrelia, Roberto Tonelli
Summary: Neuroblastoma is one of the most deadly cancers in children, with high-risk neuroblastoma (HR-NB) showing a very aggressive pattern and poor prognosis. The review focuses on the role of MYCN in HR-NB and highlights the current knowledge in diagnosis, prognosis, and therapeutic approaches. MYCN is considered a highly relevant target for HR-NB patient management, and new therapies targeting it are being proposed.
Article
Multidisciplinary Sciences
Zsuzsanna Nagy, Janith A. Seneviratne, Maxwell Kanikevich, William Chang, Chelsea Mayoh, Pooja Venkat, Yanhua Du, Cizhong Jiang, Alice Salib, Jessica Koach, Daniel R. Carter, Rituparna Mittra, Tao Liu, Michael W. Parker, Belamy B. Cheung, Glenn M. Marshall
Summary: The gain of 17q21-ter in neuroblastoma leads to overexpression of ALYREF, which forms a complex with MYCN and regulates MYCN stability via the deubiquitinating enzyme, USP3.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Soraya Epp, Shin Mei Chuah, Melinda Halasz
Summary: This review examines the intricate interplay between MYCN and known epigenetic mechanisms in neuroblastoma, and provides insights into emerging therapeutic strategies targeting these mechanisms to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jorg Otte, Cecilia Dyberg, Adena Pepich, John Inge Johnsen
Summary: Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma and is a strong predictor of poor prognosis. Increased MYCN expression is an early event in these cancers, leading to a peculiar dysregulation of cells that exhibit embryonal or cancer stem-like qualities.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Hai-Feng Zhang, Alberto Delaidelli, Sumreen Javed, Busra Turgu, Taylor Morrison, Christopher S. Hughes, Xiaqiu Yang, Manideep Pachva, Michael M. Lizardo, Gurdeep Singh, Jennifer Hoffmann, Yue Zhou Huang, Khushbu Patel, Rawan Shraim, Sonia H. Y. Kung, Gregg B. Morin, Samuel Aparicio, Daniel Martinez, John M. Maris, Kristopher R. Bosse, Karla C. Williams, Poul H. Sorensen
Summary: This study reveals that GREB1 gene, located near MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in high-risk neuroblastoma (NB). The research also identifies MYO1B gene as a crucial regulator of invasion and metastasis in MYCN amplified NB. Furthermore, MYO1B is found to regulate secretome reprogramming and the cytokine MIF mediates its pro-invasive and pro-metastatic activity.
Review
Oncology
Swapnil Parashram Bhavsar
Summary: Oncogenic drivers like MYCN in neuroblastoma subsets pose a significant challenge due to their strong correlation with high-risk metastatic disease and poor prognosis. However, the functional role of MYCN and its regulatory partners in neuroblastoma metastasis has only been partially elucidated. This minireview summarizes the recent progress in understanding their roles.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Mohit Bansal, Anamika Gupta, Han-Fei Ding
Summary: Metabolic reprogramming plays a crucial role in high-risk neuroblastoma and offers potential therapeutic opportunities. This review summarizes the recent progress in understanding neuroblastoma metabolic reprogramming and highlights important areas for future research.
Article
Oncology
Man Xu, Ming Sun, Xiyuan Zhang, Rosa Nguyen, Haiyan Lei, Jack F. Shern, Carol J. Thiele, Zhihui Liu
Summary: This study reveals a core transcriptional regulatory network in noradrenergic neuroblastoma, involving transcription factors PHOX2B, HAND2, GATA3, and MYCN. MYCN can bind to enhancers as well as promoters when aberrantly upregulated. HAND2 regulates chromatin accessibility and assists MYCN in enhancer invasion. Targeting both MYCN and the core regulatory factors can effectively suppress tumor growth.
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
Oncology
Yang Zhou, Hui Yan, Qiang Zhou, Penggao Wang, Fang Yang, Ziqiao Yuan, Qianming Du, Bo Zhai
Summary: The study found that CCNB1IP1 is upregulated in MYCN-amplified neuroblastoma and is associated with poor prognosis. CCNB1IP1 cooperates with MYCN to promote proliferation and tumorigenicity in neuroblastoma. This study also revealed a previously uncharacterized mechanism of CCNB1IP1-mediated MYCN protein stability, providing new prospects for precise treatment of MYCN-amplified neuroblastoma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Kezhe Tan, Jialin Mo, Meng Li, Yu Dong, Yujie Han, Xi Sun, Yingxuan Ma, Kai Zhu, Wei Wu, Li Lu, Jiangbin Liu, Kewen Zhao, Lei Zhang, Yujie Tang, Zhibao Lv
Summary: This study reveals the important role of SMAD9 in neuroblastoma and its positive transcriptional feedback loop with MYCN, representing a unique tumor dependency for MYCN-amplified neuroblastoma.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Felix Schmitt-Hoffner, Sjoerd van Rijn, Umut H. Toprak, Monika Mauermann, Felix Rosemann, Anke Heit-Mondrzyk, Jens-Martin Hubner, Aylin Camgoz, Sabine Hartlieb, Stefan M. Pfister, Kai-Oliver Henrich, Frank Westermann, Marcel Kool
Summary: Activation of FOXR2 identifies a subset of neuroblastoma tumors with unfavorable outcomes, potentially related to MYCN; The study confirms the importance of FOXR2 in neuroblastoma through data analysis and cell experiments, indicating its involvement in cell cycle, growth, and death; FOXR2 stabilizes MYCN protein, impacting patient clinical outcomes.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
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
Danny Misiak, Sven Hagemann, Jessica L. Bell, Bianca Busch, Marcell Lederer, Nadine Bley, Johannes H. Schulte, Stefan Huttelmaier
Summary: MYCN gene amplification and upregulated expression are critical in high-risk neuroblastoma progression. MYCN is tightly regulated in neuroblastoma, including post-transcriptional control and modulation of microRNA expression. Dysregulation of MYCN expression and miRNAs is associated with neuroblastoma pathogenesis, with potential implications for therapeutic targeting.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Hamed Alborzinia, Andres F. Florez, Sina Kreth, Lena M. Brueckner, Umut Yildiz, Moritz Gartlgruber, Dorett Odoni, Gernot Poschet, Karolina Garbowicz, Chunxuan Shao, Corinna Klein, Jasmin Meier, Petra Zeisberger, Michal Nadler-Holly, Matthias Ziehm, Franziska Paul, Juergen Burhenne, Emma Bell, Marjan Shaikhkarami, Roberto Wuerth, Sabine A. Stainczyk, Elisa M. Wecht, Jochen Kreth, Michael Buettner, Naveed Ishaque, Matthias Schlesner, Barbara Nicke, Carlo Stresemann, Maria Llamazares-Prada, Jan H. Reiling, Matthias Fischer, Ido Amit, Matthias Selbach, Carl Herrmann, Stefan Woelfl, Kai-Oliver Henrich, Thomas Hoefer, Andreas Trumpp, Frank Westermann
Summary: The study reveals that MYCN-amplified neuroblastoma undergoes ferroptosis in the absence of cysteine, suggesting a potential therapeutic approach of combining cysteine depletion and GPX4 inactivation. In addition, the study provides evidence that targeting multiple ferroptosis targets can be a promising therapeutic strategy for aggressive MYCN-amplified tumors.
