Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway
Abstract Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. However, the underlying mechanisms remain unclear. This study aimed to determine the optimal concentration of Tamibaro...
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BMC
2025-07-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-025-00962-8 |
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| author | Junjiao Zhang Wenshu XiangWei Fan Zhang Huan Yi Wei Yan Xiao Li Kai Gao Yuwu Jiang |
| author_facet | Junjiao Zhang Wenshu XiangWei Fan Zhang Huan Yi Wei Yan Xiao Li Kai Gao Yuwu Jiang |
| author_sort | Junjiao Zhang |
| collection | DOAJ |
| description | Abstract Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. However, the underlying mechanisms remain unclear. This study aimed to determine the optimal concentration of Tamibarotene (Am80) for promoting neuronal differentiation and to elucidate the underlying molecular mechanisms. SH-SY5Y cells were treated with Am80 at various concentrations, and the effects on cell morphology, gene expression, cell proliferation and apoptosis assessed using immunofluorescence, Western blotting, qPCR, and RNA sequencing. Results indicated that that 1µM Am80 effectively promoted neuronal differentiation, upregulating neuronal markers and the KCNT1 gene, while downregulating tumor-related genes MYC and CXCR4. The differentially expressed genes are predominantly enriched in the PI3K-Akt signaling pathway, with upregulation of genes related to neuronal development such as NTRK2, RET, and CNR1, and downregulation of tumor-related genes including MYC and CXCR4. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases. Graphical abstract |
| format | Article |
| id | doaj-art-7c9e8847b57f4595beaf5316fa8f17ac |
| institution | DOAJ |
| issn | 1471-2202 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj-art-7c9e8847b57f4595beaf5316fa8f17ac2025-08-20T03:04:15ZengBMCBMC Neuroscience1471-22022025-07-0126111210.1186/s12868-025-00962-8Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathwayJunjiao Zhang0Wenshu XiangWei1Fan Zhang2Huan Yi3Wei Yan4Xiao Li5Kai Gao6Yuwu Jiang7Children’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalChildren’s Medical Center, Peking University First HospitalAbstract Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. However, the underlying mechanisms remain unclear. This study aimed to determine the optimal concentration of Tamibarotene (Am80) for promoting neuronal differentiation and to elucidate the underlying molecular mechanisms. SH-SY5Y cells were treated with Am80 at various concentrations, and the effects on cell morphology, gene expression, cell proliferation and apoptosis assessed using immunofluorescence, Western blotting, qPCR, and RNA sequencing. Results indicated that that 1µM Am80 effectively promoted neuronal differentiation, upregulating neuronal markers and the KCNT1 gene, while downregulating tumor-related genes MYC and CXCR4. The differentially expressed genes are predominantly enriched in the PI3K-Akt signaling pathway, with upregulation of genes related to neuronal development such as NTRK2, RET, and CNR1, and downregulation of tumor-related genes including MYC and CXCR4. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases. Graphical abstracthttps://doi.org/10.1186/s12868-025-00962-8TamibaroteneSH-SY5YCell differentiationKCNT1PI3K/Akt signaling pathway |
| spellingShingle | Junjiao Zhang Wenshu XiangWei Fan Zhang Huan Yi Wei Yan Xiao Li Kai Gao Yuwu Jiang Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway BMC Neuroscience Tamibarotene SH-SY5Y Cell differentiation KCNT1 PI3K/Akt signaling pathway |
| title | Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway |
| title_full | Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway |
| title_fullStr | Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway |
| title_full_unstemmed | Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway |
| title_short | Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway |
| title_sort | tamibarotene promotes differentiation of neuroblastoma sh sy5y cells into neurons which is associated with activation of the pi3k akt signaling pathway |
| topic | Tamibarotene SH-SY5Y Cell differentiation KCNT1 PI3K/Akt signaling pathway |
| url | https://doi.org/10.1186/s12868-025-00962-8 |
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