急性髓系白血病（AML）是一种高发的异质性血液恶性肿瘤，通常采用大剂量常规化疗药物进行强化和维持治疗。然而，细胞耐药性仍然是一个尚未解决的问题。 miRNAs的异常表达与AML的发病、进展密切相关，并影响癌细胞的耐药性。 miR-149-3p在癌细胞对顺铂的耐药中发挥重要作用，发挥优异的抗肿瘤活性。通过研究miR-149-3p的功能，有望找到逆转化疗耐药的新治疗方法。为了探讨miR-149-3p对AML化疗药物敏感性的作用机制，我们探讨了Warburg效应与AML化疗耐药之间的关系。以AML细胞为基础，转染miR-149-3p抑制剂/NC和Warburg效应抑制剂（2DG）和PI3K/AKT通路抑制剂（LY294002），探讨IFN-γ通过Warburg效应调节AML细胞化疗耐药的机制。 miR-149-3p 的下调显着抑制 AML 细胞的药物敏感性。 miR-149-3p的下调显着促进AML细胞的增殖和侵袭，同时通过上调Bcl-2的表达和下调Bax的表达来抑制细胞凋亡。 miR-149-3p的下调显着促进Warburg效应相关蛋白己糖激酶2（HK2）、乳酸脱氢酶A（LDHA）和葡萄糖转运蛋白1（GLUT1）的表达、葡萄糖消耗、乳酸和细胞内ATP的产生。用2DG抑制Warburg效应后，miR-149-3p的效应被抑制，表明miR-149-3p的上调通过抑制Warburg效应逆转了AML细胞的耐药性。此外，miR-149-3p 与 AKT1 相互作用。 miR-149-3p 的下调会增加肌苷磷酸 3 激酶 (PI3K)、蛋白激酶 B (AKT) 和多药耐药蛋白 (MDR1) 的表达。 LY294002抑制这些蛋白的表达，下调miR-149-3p逆转了LY294002的作用，提高了细胞的耐药性。 miR-149-3p 表达的上调可能是 AML 耐药的潜在治疗靶点。它已被证明可以抑制 PI3K/AKT 通路激活，从而抑制 Warburg 效应，并影响细胞增殖、凋亡和耐药性。© 2024。作者，获得 Springer Science Business Media, LLC 的独家许可，部分施普林格自然。

Acute myeloid leukemia (AML) is a kind of heterogeneous hematologic malignancy with high incidence, which is usually treated by intensive and maintenance treatment with large dose of conventional chemotherapy drugs. However, cell resistance is still an unsolved problem. The abnormal expression of miRNAs is closely related to the pathogenesis and progression of AML, and affects the drug resistance of cancer cells. miR-149-3p plays an important role in the resistance of cancer cells to cisplatin, and plays an excellent anti-tumor activity. By studying the function of miR-149-3p, it is expected to find new therapeutic methods to reverse chemotherapy resistance. In order to explore the mechanism of action of miR-149-3p on AML chemotherapeutic drug sensitivity, we explored the relationship between the Warburg effect and AML chemotherapeutic drug resistance. Based on AML cells, transfection of miR-149-3p inhibitor/NC and Warburg effect inhibitor (2DG) and PI3K/AKT pathway inhibitor (LY294002) were used to investigate the mechanism of IFN-γ regulating chemotherapy resistance of AML cells through Warburg effect. Down-regulation of miR-149-3p significantly inhibited drug sensitivity of AML cells. Down-regulation of miR-149-3p significantly promoted proliferation and invasion of AML cells while inhibiting apoptosis by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax. Down-regulation of miR-149-3p significantly promoted the expression of Warburg effect-related proteins hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and Glucose transporter 1 (GLUT1), glucose consumption, lactic acid, and intracellular ATP production. After inhibiting the Warburg effect with 2DG, the effect of miR-149-3p was inhibited, suggesting that upregulation of miR-149-3p reversed AML cell resistance by inhibiting the Warburg effect. In addition, miR-149-3p interacted with AKT1. Down-regulation of miR-149-3p increased the expression of inosine phosphate 3 kinase (PI3K), protein kinase B (AKT), and multi-drug resistance protein (MDR1). LY294002 inhibited the expression of these proteins, and down-regulation of miR-149-3p reversed the effect of LY294002 and improved the drug resistance of cells. Upregulation of miR-149-3p expression may potentially be a therapeutic target for AML resistance. It has been shown to inhibit PI3K/AKT pathway activation, thereby inhibiting the Warburg effect, and affecting cell proliferation, apoptosis, and drug resistance.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.