Language
English
Publication Date
1-1-2026
Journal
Theranostics
DOI
10.7150/thno.120935
PMID
41510169
PMCID
PMC12775802
PubMedCentral® Posted Date
1-1-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Rationale: Neuroblastoma (NB) is a predominant extra-cranial malignancy in childhood, while molecular drivers of its progression and effective treatment strategies have yet to be clarified.
Methods: RNA sequencing was performed to identify transcriptional regulators and corresponding target genes. To explore the biological effects and underlying mechanisms of these regulators, a comprehensive methodology was utilized, encompassing chromatin immunoprecipitation, dual-luciferase reporter assay, qRT-PCR, western blot, alongside gene over-expression and silencing techniques, co-immunoprecipitation, and mass spectrometry. The MTT assay, soft agar colony formation, Matrigel invasion, and nude mouse xenograft models were applied to assess oncogenic properties. Patient survival was analyzed using the log-rank test.
Results: Armadillo repeat containing 12 (ARMC12) was identified as a MYC-interacting modulator within liquid condensates to up-regulate critical nucleoporin-encoding targets (NUP62/NUP93/NUP98), which promoted nuclear pore complex (NPC) biogenesis to facilitate nuclear trafficking of oncogenic effectors, thereby enhancing invasion and metastasis of NB. As a protein within extracellular vesicles of Malassezia globosa colonizing NB tissues, MGL_0381 also facilitated MYC transactivation via physical interaction to accelerate NPC biogenesis and NB progression. Tioconazole (TCZ) and UU-T02 were identified as efficient inhibitors blocking ARMC12-MYC and MGL_0381-MYC interaction, and synergistically reduced NPC number and aggressive features of NB. High ARMC12, MYC, NUP62, NUP93, or NUP98 levels served as markers of unfavorable patient outcomes in clinical cohorts.
Conclusions: These findings collectively demonstrate that dual targeting of AMRC12 and Malassezia globosa disrupts MYC liquid condensates-driven NPC biogenesis during NB progression.
Keywords
Animals, Humans, Proto-Oncogene Proteins c-myc, Cell Line, Tumor, Neuroblastoma, Mice, Malassezia, Nuclear Pore, Mice, Nude, Gene Expression Regulation, Neoplastic, Nuclear Pore Complex Proteins, neuroblastoma, armadillo repeat containing 12, MYC, Malassezia globosa, nuclear pore complex
Published Open-Access
yes
Recommended Citation
Hu, Anpei; Yang, Chunhui; Wang, Zhijie; et al., "Dual Targeting of AMRC12 and Malassezia globosa Disrupts MYC Liquid Condensates-Driven Nuclear Pore Complex Biogenesis in Neuroblastoma" (2026). Faculty, Staff and Students Publications. 8275.
https://digitalcommons.library.tmc.edu/baylor_docs/8275