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丹参酮提取物通过加速 microRNA-211-5p 抑制 Janus 激酶 2/信号转导和转录激活因子 3 信号通路的激活,刺激小儿急性髓系白血病干细胞凋亡和抗炎机制。

Cryptanshinone extract of Salvia miltiorrhiza stimulates pediatric acute myeloid leukemia stem cell apoptosis and the anti-inflammatory mechanism via accelerating microRNA-211-5p to supress Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway activation.

机构信息

Department of Pharmacy, Chunan County Traditional Chinese Medicine Hospital, Hangzhou, Zhejiang Province, China.

Department of Surgery, Chun'an County Weiping Central Health Center, Hangzhou, Zhejiang Province, China.

出版信息

J Physiol Pharmacol. 2023 Dec;74(6). doi: 10.26402/jpp.2023.6.09. Epub 2024 Feb 7.

Abstract

This study was designed to explore cryptanshinone (CPT) extract of Salvia miltiorrhiza stimulating pediatric acute myeloid leukemia (AML) stem cell (LSC) apoptosis and anti-inflammatory mechanism via accelerating microRNA (miR)-211-5p to restrain Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway activation. Obtaining blood samples from pediatric acute myeloid leukemia patients and healthy volunteers and detecting miR-211-5p and JAK2 were performed. Purchase of the human AML cell line KG1a was conducted, and sorting of KG1a cells was to gain LSC. Test of miR-211-5p and JAK2, the phosphorylation of JAK2/STAT3 was implemented. Pretreatment of LSCs was with CPT. Variation of miR-211-5p and JAK2 in LSCs was via plasmid transfection to explore their actions in cell advancement with apoptosis and inflammation. Identification of the targeting of miR-211-5p with JAK2 was implemented. In results: MiR-211-5p was declined in endometrial cancer, while JAK2 was elevated; CPT was available to boost LSC apoptosis and restrain the inflammation; elevated miR-211-5p or repressive JAK2 was available to strengthen the acceleration of CPT on LSCs apoptosis and the repression of inflammation; MiR-211-5p targeted JAK2; augmented JAK2 was available to turn around the action of elevated miR-211-5p. We conclude that CPT extract of Salvia miltiorrhiza stimulated pediatric LSC apoptosis and restrained the inflammation via accelerating microRNA (miR)-211-5p to suppress JAK2/STAT3 pathway activation.

摘要

本研究旨在探讨丹参酮(CPT)提取物通过加速 microRNA(miR)-211-5p 抑制 Janus 激酶 2(JAK2)/信号转导和转录激活因子 3(STAT3)通路激活,刺激小儿急性髓系白血病(AML)干细胞(LSC)凋亡和抗炎的机制。从小儿急性髓系白血病患者和健康志愿者中获取血液样本,并检测 miR-211-5p 和 JAK2。购买人 AML 细胞系 KG1a,并对 KG1a 细胞进行分选以获得 LSC。检测 miR-211-5p 和 JAK2,JAK2/STAT3 的磷酸化。对 LSCs 进行 CPT 预处理。通过质粒转染改变 LSCs 中的 miR-211-5p 和 JAK2,探讨它们在细胞进展和凋亡及炎症中的作用。实施 miR-211-5p 与 JAK2 的靶向鉴定。结果:miR-211-5p 在子宫内膜癌中下降,而 JAK2 升高;CPT 可促进 LSC 凋亡并抑制炎症;上调 miR-211-5p 或抑制 JAK2 可增强 CPT 对 LSCs 凋亡的加速作用和炎症的抑制作用;miR-211-5p 靶向 JAK2;上调 JAK2 可逆转上调 miR-211-5p 的作用。我们得出结论,丹参酮提取物通过加速 microRNA(miR)-211-5p 抑制 JAK2/STAT3 通路激活,刺激小儿 LSC 凋亡并抑制炎症。

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