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July 2nd, 2025
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NATIONAL BRAIN RESEARCH CENTRE
neuroscience
biorxiv

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

KRISHNA, S.Open in Google Scholar•KUMARI, M.Open in Google Scholar

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 Wnt3a 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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