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bioRxiv · 10.64898/2026.10.24.761494

Anti-Nucleolin Aptamer iSN04 Inhibits Alveolar Rhabdomyosarcoma Cell Growth by Inducing Myogenic Differentiation

Saitoh, Y.·Takaya, T.
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Abstract

Rhabdomyosarcoma (RMS) is a muscle-derived soft tissue tumor that retains myogenic potential. Novel drugs for RMS are strongly needed because the standard chemotherapeutic agents for RMS, including vincristine (VCR), have marginally improved the survival rate of high-risk patients for several decades. An anti-nucleolin aptamer, iSN04, was originally identified to promote myogenic differentiation of myoblasts, and was subsequently reported to suppress the growth of embryonal RMS cells by potentiating their differentiation and arresting proliferation. The present study investigated the effects of iSN04 on two alveolar RMS cell lines, NRS-1 and RH30. iSN04 modulated gene expression levels such as myogenic transcription factors (MyoD and myogenin), inhibitor of differentiation proteins (ID1 and ID3), and the tumor suppressor CASZ1. iSN04 treatment induced NRS-1 cells to differentiate into contracting myotube-like cells, and severely impaired the ability of RH30 cells to form and grow tumorspheres in three-dimensional culture. Co-treatment with iSN04 and a low dose of VCR cooperatively suppressed the proliferation of RH30 cells compared with single-agent treatments. These data demonstrate that iSN04 can be a beneficial agent for RMS and hold potential for use in combination therapy with current standard drugs.

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Saitoh, Y., Takaya, T.. 2026-10-27. Anti-Nucleolin Aptamer iSN04 Inhibits Alveolar Rhabdomyosarcoma Cell Growth by Inducing Myogenic Differentiation. https://doi.org/10.64898/2026.10.24.761494

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