ArticleMedical oncology (Northwood, London, England)2025
Effects of APT20TTMG, a modulator of the U1 snRNP complex, in glioblastoma models.
Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The U1 small nuclear ribonucleoprotein (snRNP) complex is essential for pre-mRNA splicing and inhibition of premature polyadenylation. Its dysfunction has been implicated in various cancers, including glioblastoma, driving oncogenic splicing and tumor progression. This study explored the potential of APT20TTMG, a synthetic cDNA that modulates U1 snRNP misassembly, in glioblastoma. The internalization of APT20TTMG was assessed in U-87 MG cells, as well as its effects on cell viability, proliferation, and apoptosis. Athymic mice were used to evaluate the effects of intravenous APT20TTMG administration on tumor-related parameters. APT20TTMG exhibited over 50% internalization, exerting cytotoxic, cytostatic, and pro-apoptotic effects in vitro. A 22-day treatment with APT20TTMG reduced tumor volume, slowed tumor growth, and showed a trend toward increased body weight. Treatment also decreased oncogenic pathways and tended to enhance histopathological outcomes. A pilot study combining APT20TTMG with temozolomide further improved antitumor efficacy. Our results demonstrate that APT20TTMG has strong potential in correcting U1 snRNP complex dysfunction, supporting its further investigation as a strategy to modulate splicing in glioblastoma.
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