Research progress of HOX genes in spinal ependymal tumors

doi:10.3969/j.issn.1006-7795.2026.03.015

Abstract

Abstract: HOX genes constitute a highly conserved family of homeobox genes, which play a crucial role in embryonic development, cell differentiation, and tissue homeostasis. Abnormal expression of these genes is closely related to the occurrence, development, and prognosis of various tumors. Increasing evidence suggests that the dysregulation of HOX genes may play an important role in the occurrence, development, and invasiveness of spinal meningeal tumors. This article reviews the regulatory mechanisms of HOX genes, their expression patterns in spinal meningeal tumors, and their potential clinical value. Finally, this review outlines directions for future research.

Key words: HOX genes, spinal cord ependymoma, myxopapillary ependymoma, regulatory mechanism, expression features, clinical value

CLC Number:

R365，R361，R363，R364.7

Wang Wanting, Wang Leiming, Teng Lianghong. Research progress of HOX genes in spinal ependymal tumors[J]. Journal of Capital Medical University, 2026, 47(3): 527-531.

References

［1］Hubert K A, Wellik D M. Hox genes in development and beyond［J］. Development, 2023, 150(1): dev192476.
［2］Economides K D, Zeltser L, Capecchi M R. Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae［J］. Dev Biol, 2003, 256(2): 317-330.
［3］Shah N, Sukumar S. The Hox genes and their roles in oncogenesis［J］. Nat Rev Cancer, 2010, 10(5): 361-371.
［4］Koester S W, Lu V M, Basil G W. Letter: predictors of progression-free survival in patients with spinal intramedullary ependymoma: a multicenter retrospective study by the Neurospinal Society of Japan［J］. Neurosurgery, 2023, 93(5): e146-e147.
［5］Gilbert M R, Ruda R, Soffietti R. Ependymomas in adults［J］. Curr Neurol Neurosci Rep, 2010, 10(3): 240-247.
［6］Ellison D W, Aldape K D, Capper D, et al. cIMPACT-NOW update 7: advancing the molecular classification of ependymal tumors［J］. Brain pathology, 2020 Sep，30(5):863-866.
［7］Wei M K, Qin Z K, Kong D X, et al. Echiuran Hox genes provide new insights into the correspondence between Hox subcluster organization and collinearity pattern［J］. Proc Biol Sci, 2022, 289(1982): 20220705.
［8］Peraldi R, Kmita M. 40 years of the homeobox: mechanisms of Hox spatial-temporal collinearity in vertebrates［J］. Development, 2024, 151(16): dev202508.
［9］Aguilar-Camacho J M, Harry N D, Zakas C. Comparative Hox genes expression within the dimorphic annelid Streblospio benedicti reveals patterning variation during development［J］. Evodevo, 2024, 15(1): 12.
［10］Miller A, Dasen J S. Establishing and maintaining Hox profiles during spinal cord development［J］. Semin Cell Dev Biol, 2024, 152/153: 44-57.
［11］Hu X, Wang Y, Zhang X Y, et al. DNA methylation of HOX genes and its clinical implications in cancer［J］. Exp Mol Pathol, 2023, 134: 104871.
［12］Benetti N, Gouil Q, Tapia Del Fierro A, et al. Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo［J］. Nat Commun, 2022, 13(1): 4295.
［13］He J, Li L, Wang S X, et al. Abnormal methylation of HOXA11 promoter promotes tumor progression in testicular germ cell tumor［J］. Am J Transl Res, 2024, 16(5): 1660-1668.
［14］De Bessa Garcia S A, Araújo M, Pereira T, et al. HOX genes function in breast cancer development［J］. Biochim Biophys Acta Rev Cancer, 2020, 1873(2): 188358.
［15］Jambhekar A, Dhall A, Shi Y. Roles and regulation of histone methylation in animal development［J］. Nat Rev Mol Cell Biol, 2019, 20(10): 625-641.
［16］Hawkins R D, Hon G C, Lee L K, et al. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells［J］. Cell Stem Cell, 2010, 6(5): 479-491.
［17］Quaas C E, Lin B C, Long D T. Transcription suppression is mediated by the HDAC1-Sin3 complex in Xenopus nucleoplasmic extract［J］. J Biol Chem, 2022, 298(11): 102578.
［18］Lee H, Machado C R L, Hammaker D, et al. Joint-specific regulation of homeobox D10 expression in rheumatoid arthritis fibroblast-like synoviocytes［J］. PLoS One, 2024, 19(6): e0304530.
［19］Ahmad F, Sudesh R, Ahmed A T, et al. The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget［J］. Expert Rev Mol Med, 2024, 26: e11.
［20］Turetzek N, Pechmann M, Janssen R, et al. Hox genes in spiders: their significance for development and evolution［J］. Semin Cell Dev Biol, 2024, 152/153: 24-34.
［21］Lourdusamy A, Rahman R, Grundy R G. Expression alterations define unique molecular characteristics of spinal ependymomas［J］. Oncotarget, 2015, 6(23): 19780-19791.
［22］Taylor M D, Poppleton H, Fuller C, et al. Radial glia cells are candidate stem cells of ependymoma［J］. Cancer Cell, 2005, 8(4): 323-335.
［23］Kim K T, Lee C H, Chung C K, et al. Is NF2 a key player of the differentially expressed gene between spinal cord ependymoma and intracranial ependymoma?［J］. World Neurosurg, 2018, 118: e906-e917.
［24］Palm T, Figarella-Branger D, Chapon F, et al. Expression profiling of ependymomas unravels localization and tumor grade-specific tumorigenesis［J］. Cancer, 2009, 115(17): 3955-3968.
［25］Zheng H Y, Baranova K, Song J, et al. Overexpression of long noncoding RNA HOTAIR is a unique epigenetic characteristic of myxopapillary ependymoma［J］. J Neuropathol Exp Neurol, 2020, 79(11): 1193-1202.
［26］Gu S X, Gu W T, Shou J J, et al. The molecular feature of HOX gene family in the intramedullary spinal tumors［J］. Spine, 2017, 42(5): 291-297.
［27］Barton V N, Donson A M, Kleinschmidt-DeMasters B K, et al. Unique molecular characteristics of pediatric myxopapillary ependymoma［J］. Brain Pathol, 2010, 20(3): 560-570.
［28］Purkait S, Praeger S, Felsberg J, et al. Strong nuclear expression of HOXB13 is a reliable surrogate marker for DNA methylome profiling to distinguish myxopapillary ependymoma from spinal ependymoma［J］. Acta Neuropathol, 2025, 149(1): 29.
［29］Wang H, Zhang S, Rehman S K, et al. Clinicopathological features of myxopapillary ependymoma［J］. J Clin Neurosci, 2014, 21(4): 569-573.
［30］Bockmayr M, Harnisch K, Pohl L C, et al. Comprehensive profiling of myxopapillary ependymomas identifies a distinct molecular subtype with relapsing disease［J］. Neuro Oncol, 2022, 24(10): 1689-1699.
［31］Carpenter E M. Hox genes and spinal cord development［J］. Dev Neurosci, 2002, 24(1): 24-34.
［32］Niederreither K, McCaffery P, Dräger U C, et al. Res-tricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse development［J］. Mech Dev, 1997, 62(1): 67-78.
［33］Neijts R, Amin S, Van Rooijen C, et al. Cdx is crucial for the timing mechanism driving colinear Hox activation and defines a trunk segment in the Hox cluster topology［J］. Dev Biol, 2017, 422(2): 146-154.
［34］Liu C, Xie Y X, Chen X Y, et al. BAF45D-binding to HOX genes was differentially targeted in H9-derived spinal cord neural stem cells［J］. Sci Rep, 2024, 14(1): 29.
［35］Schumann Y, Dottermusch M, Schweizer L, et al. Morphology-based molecular classification of spinal cord ependymomas using deep neural networks［J］. Brain Pathol, 2024, 34(5): e13239.
［36］Vazquez I E, Ducray F. The role of radiotherapy, chemotherapy, and targeted therapies in adult intramedullary spinal cord tumors［J］. Cancers, 2024, 16(16): 2781.
［37］Rudà R, Bruno F, Pellerino A, et al. Ependymoma: evaluation and management updates［J］. Curr Oncol Rep, 2022, 24(8): 985-993.
［38］Cerretti G, Pessina F, Franceschi E, et al. Spinal ependymoma in adults: from molecular advances to new treatment perspectives［J］. Front Oncol, 2023, 13: 1301179.

[1]	Du Juan, Che Jialu, Yan Guangxuan, Su Dan, Che Nanying. Analysis of clinical and histopathological features of brucella spondylitis and diagnostic value of novel molecular pathological techniques [J]. Journal of Capital Medical University, 0, (): 482-489.
[2]	Zhu Meiling, Qiu Mingxin, Hong Shan, Liu Feifei, Yue Wenhui, Chen Jiamin, Cheng Jun, Sun Lei. A study on the clinicopathological characteristics of gastrointestinal sexually transmitted diseases [J]. Journal of Capital Medical University, 2026, 47(3): 497-506.
[3]	Yang Min, An Guo, Zhao Wei, Ma Yuanyuan. Pathological mechanism study on the colitis mice model [J]. Journal of Capital Medical University, 2018, 39(5): 704-709.
[4]	Zhuang Xiaoming;Zhao Zhiwei;Ji Zhijuan;Zhao Yongmei;Sheng Shuli . Effect of APP17 Peptide on the Hippocampal Neurons Ultrastructure and Expression of InsR, Ins-1 in Type 2 Diabetic KKAy Mice [J]. Journal of Capital Medical University, 2002, 23(2): 115-118.
[5]	Liu Fan;Chen Ruifen;Liu Guozhen;Song Aili. Mechanism of Pulmonary Vascular Structure Remodeling Induced by Chronic Hypoxia [J]. Journal of Capital Medical University, 1999, 20(1): 28-31.
[6]	Xu Qingzhong;Duan Huiling;Lu Dehong. Immunohistochemical Study of PCNA in Cerebral Astrocytomas [J]. Journal of Capital Medical University, 1997, 18(4): 321-323.
[7]	Wen Xiangyun;Yang Peixun;Zhou Yijian. The Influence of Skin Overlay at the Wound Surface on the Tendon Repair after Burn [J]. Journal of Capital Medical University, 1994, 15(1): 31-33.
[8]	Chen Ruifen;Chen Tiejun;Zheng Guofen;Yang Jie;Zhang Yongchun. The Etiology of Chorioangiosis [J]. Journal of Capital Medical University, 1993, 14(4): 258-260.
[9]	Dong Shiqin;Wang Jie;Yu Hengxi;Yue Xiaohui;Fan Lili. An Puerarin Cardioplegic Solution on Electron Microscopic Observation of the Protecdtive Effect of Hypothermic and Global Ischemic Myocardium [J]. Journal of Capital Medical University, 1992, 13(3): 190-194.