PTTG1 inhibition suppresses proliferation and promotes neuroblastoma differentiation via autophagy [Oral presentation]

Abstract

<p><strong>Purpose:</strong> Pituitary tumor-transforming gene 1 (PTTG1), an established oncogene overexpressed in multiple cancers including neuroblastoma (NB) and implicated in cell cycle regulation, remains incompletely characterized in NB pathogenesis.</p><p><strong>Methods:</strong> PTTG1 expression was analyzed in NB cell lines. siRNA-mediated PTTG1 knockdown was performed, followed by functional assays: CCK-8 and EdU for proliferation; wound healing and transwell for migration/invasion. Protein/mRNA expression of migration (MMP2, MMP9, GAP43, TH, MEG), differentiation (TUBB3), and autophagy markers (LC3II/I, beclin1, P62, mTOR) was assessed via Western blotting, PCR, and immunofluorescence. Mechanistic studies employed the autophagy inhibitor 3-methyladenine (3-MA).</p><p><strong>Results:</strong> PTTG1 was significantly overexpressed across NB cell lines, highest in SK-N-SH. PTTG1 silencing in SK-N-SH cells potently inhibited proliferation, migration, and invasion, concomitant with reduced MMP2/9 protein. Knockdown increased TUBB3 (differentiation) and LC3II (autophagy) immunofluorescence intensity. Protein/mRNA levels of GAP43, TH, MEG, TUBB3, LC3II/I, and beclin1 were upregulated, while P62 and mTOR were downregulated. Critically, 3-MA treatment attenuated the PTTG1 knockdown-induced suppression of proliferation and promotion of differentiation.</p><p><strong>Conclusion</strong>: This study demonstrates significant PTTG1 overexpression in NB cells. PTTG1 knockdown induces autophagy, suppressing SK-N-SH proliferation and promoting differentiation. These effects are mechanistically linked to autophagy, as evidenced by 3-MA reversal, identifying PTTG1 as a potential therapeutic target for NB.</p>