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Theranostics 2021; 11(12):5831-5846. doi:10.7150/thno.55574 This issue Cite

Research Paper

Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling

Kaiju Sun1, Yangyang Du2, Yuzhu Hou1, Mingyue Zhao1, Jiajia Li3, Yazhe Du4, Lingxiao Zhang2, Changbao Chen1, Hongmei Yang1, Fei Yan2✉, Rui Su1✉

1. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130017, China.
2. State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
3. Department of Obstetrics and Gynecology, First Hospital, Jilin University, 130021, P. R. China.
4. Department of blood specialty, First Hospital, Jilin University, 130021, China.

✉ Corresponding authors: F. Y (E-mail: feiyanedu.cn) or R. S. (E-mail: sranalchemcom).

Citation:
Sun K, Du Y, Hou Y, Zhao M, Li J, Du Y, Zhang L, Chen C, Yang H, Yan F, Su R. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics 2021; 11(12):5831-5846. doi:10.7150/thno.55574. https://www.thno.org/v11p5831.htm
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Abstract

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Purpose: The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N6-methyladenosine (m6A) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the m6A demethylation activity by targeting FTO of SsD.

Methods: It was examined whether and how SsD regulates FTO/m6A signaling in AML. The pharmacologic activities and mechanisms of actions of SsD in vitro, in mice, primary patient cells, and tyrosine kinase inhibitors-resistant cells were determined.

Results: SsD showed a broadly-suppressed AML cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo. Mechanistically, SsD directly targeted FTO, thereby increasing global m6A RNA methylation, which in turn decreased the stability of downstream gene transcripts, leading to the suppression of relevant pathways. Importantly, SsD also overcame FTO/m6A-mediated leukemia resistance to tyrosine kinase inhibitors.

Conclusion: Our findings demonstrated that FTO-dependent m6A RNA methylation mediated the anti-leukemic actions of SsD, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy.

Keywords: Saikosaponin D, leukemia, N6-methyladenosine, FTO

Citation styles

APA
Sun, K., Du, Y., Hou, Y., Zhao, M., Li, J., Du, Y., Zhang, L., Chen, C., Yang, H., Yan, F., Su, R. (2021). Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics, 11(12), 5831-5846. https://doi.org/10.7150/thno.55574.

ACS
Sun, K.; Du, Y.; Hou, Y.; Zhao, M.; Li, J.; Du, Y.; Zhang, L.; Chen, C.; Yang, H.; Yan, F.; Su, R. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics 2021, 11 (12), 5831-5846. DOI: 10.7150/thno.55574.

NLM
Sun K, Du Y, Hou Y, Zhao M, Li J, Du Y, Zhang L, Chen C, Yang H, Yan F, Su R. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics 2021; 11(12):5831-5846. doi:10.7150/thno.55574. https://www.thno.org/v11p5831.htm

CSE
Sun K, Du Y, Hou Y, Zhao M, Li J, Du Y, Zhang L, Chen C, Yang H, Yan F, Su R. 2021. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics. 11(12):5831-5846.

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