# Molecular and therapeutic mechanisms of differentiation-inducing microRNA miR-506-3p in neuroblastoma > **NIH NIH R15** · TEXAS STATE UNIVERSITY · 2020 · $445,639 ## Abstract Molecular and therapeutic mechanisms of differentiation-inducing microRNA miR-506-3p in neuroblastoma Abstract There is a lack of understanding how critical microRNAs (miRNAs) are in controlling neuroblastoma (NBL) cell differentiation. This prevents the application of miRNA-based therapeutics to NBL differentiation therapy, which is an approach to induce malignant cells into terminal differentiation and thereby block tumor growth. The long- term goal of the applicant is to define the role of miRNAs in regulating NBL cell differentiation and make contributions to the development of miRNA-based differentiation therapy for NBL. The objective of this study is to elucidate the mechanisms underlying the differentiation-inducing function of a differentiation-inducing miRNA recently identified in our group, miR-506-3p, and to develop miR-506-3p analogs with enhanced differentiation-inducing activity. The central hypothesis is that miR-506-3p functions as a inducer of cell differentiation through directly targeting a group of genes that play key roles in regulating NBL cell differentiation, and that miR-506-3 analogs with enhanced differentiation-inducing activity can be developed by modifying the nucleotide sequence in the non-seed region of the wildtype miR-506-3p. This hypothesis is supported by strong preliminary data generated in the applicant's lab. The following Specific Aims are proposed: Aim 1, Identify novel miR-506-3p targets that mediate its differentiation-inducing function. A functional high-content screening (HCS) approach will be used to systematically investigate its targets regarding their role in regulating NBL cell differentiation. The direct interactions of miR-506-3p with the targets identified from screen will be validated by combining a biotinylated-miRNA pull-down assay and a luciferase reporter assay. Since the molecular mechanisms of regulating NBL cell differentiation are still poorly understood, we expect that a comprehensive investigation of the miR-506-3p targets will reveal genes that were previously unknown to regulate NBL differentiation. Aim 2, Develop novel miR-506-3p analogs with enhanced differentiation-inducing activity. Synthetic analogs of miR-506-3p will be designed, and analogs with significantly increased differentiation-inducing activity relative to wildtype miR-506-3p mimic will be identified using HCS and further in vitro validation analysis. The identified analogs will then be preliminarily evaluated for their therapeutic potential by examining their generic differentiation-inducing activity in a panel of NBL cell lines with diverse genetic background, and by examining their effect on viability of non-NBL cells in order to select analogs with minimum non-specific cytotoxicity. The study is innovative because it will elucidate a novel cell differentiation pathway in NBL mediated by miR-506-3p and its target genes, and it will identify novel miRNA- 506-3p analogs that has potential to be developed as differen... ## Key facts - **NIH application ID:** 9949201 - **Project number:** 1R15CA249653-01 - **Recipient organization:** TEXAS STATE UNIVERSITY - **Principal Investigator:** Liqin Du - **Activity code:** R15 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $445,639 - **Award type:** 1 - **Project period:** 2020-09-01 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9949201 ## Citation > US National Institutes of Health, RePORTER application 9949201, Molecular and therapeutic mechanisms of differentiation-inducing microRNA miR-506-3p in neuroblastoma (1R15CA249653-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9949201. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*