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bioRxiv · 10.1101/2025.06.30.662295

A BASP1/BASP1-AS1 Axis Modulates Wnt and Notch Signaling to Balance Proliferation and Differentiation in Neuroblastoma Cells

KRISHNA, S.·KUMARI, M.
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Abstract

Neuroblastoma exhibits significant intratumoral heterogeneity and resistance to differentiation therapy. We identify a regulatory axis between the protein-coding gene BASP1 and its antisense lncRNA BASP1-AS1 as a molecular switch between proliferation and neuronal differentiation in SH-SY5Y neuroblastoma cells. BASP1 maintains a proliferative, undifferentiated state by upregulating Wnt3a signaling and stemness-associated markers. Knockdown of BASP1 inhibits both proliferation and neuronal gene expression, implicating it as a context-specific oncogenic driver. In contrast, BASP1-AS1 is transiently induced by retinoic acid (RA) and initiates early neuronal differentiation via DCX and MAP2 induction. BASP1-AS1 represses Wnt3a and activates Notch1, redirecting the signaling balance toward a differentiation-permissive state. A reciprocal suppression between BASP1 and BASP1-AS1 underlies a transition from Wnt3a to Wnt2 activity as differentiation progresses. LiCl-mediated Wnt3a activation suppresses BASP1-AS1 and reinduces Sox2, highlighting Wnt3as role in maintaining stemness and therapy resistance. Post-RA BDNF treatment reinforces terminal differentiation, defined by high BASP1-AS1, DCX, and MAP2, and loss of proliferative signatures. Together, these findings identify the BASP1/BASP1-AS1 axis as a central node integrating Wnt and Notch pathways to regulate plasticity and lineage progression in neuroblastoma. This axis represents a potential target for overcoming differentiation blockade and therapeutic resistance.

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KRISHNA, S., KUMARI, M.. 2025-07-02. A BASP1/BASP1-AS1 Axis Modulates Wnt and Notch Signaling to Balance Proliferation and Differentiation in Neuroblastoma Cells. https://doi.org/10.1101/2025.06.30.662295

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