肝癌中高表达的长链非编码 RNA 通过 miR-150-5p/MCL1 轴调节慢性髓系白血病对伊马替尼的耐药性。
LncRNA highly upregulated in liver cancer regulates imatinib resistance in chronic myeloid leukemia via the miR-150-5p/MCL1 axis.
机构信息
Department of Pharmacy, Weifang People's Hospital, Weifang, Shandong, China.
出版信息
Anticancer Drugs. 2021 Apr 1;32(4):427-436. doi: 10.1097/CAD.0000000000001019.
Chronic myeloid leukemia (CML) is a type of myeloproliferative neoplasm. Aberrant expression of long noncoding RNA highly upregulated in liver cancer (HULC) has been implicated in tumor progression, including CML. This study aimed to investigate the role of HULC in CML. The levels of HULC, miR-150-5p and myeloid cell leukemia 1 (MCL1) were examined by quantitative real-time PCR or western blot assay. Cell counting kit-8 assay was used to detect cell viability and half inhibition concentration. Cell apoptosis was monitored by flow cytometry and western blot. The interaction among HULC, miR-150-5p and MCL1 was validated by dual-luciferase reporter assay. The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phosphorylation-AKT was evaluated using western blot assay. HULC and MCL1 were upregulated, whereas miR-150-5p was downregulated in bone marrow mononuclear cells of CML patients and CML cells. HULC overexpression increased imatinib resistance in K562 cells, and HULC depletion enhanced imatinib sensitivity in imatinib-resistant cells (K562-R). Mechanically, HULC was a sponge of miR-150-5p. HULC contributed to imatinib resistance through regulation of miR-150-5p. MCL1 bound to miR-150-5p and reversed the effect of HULC on imatinib resistance. HULC regulated the PI3K/AKT pathway via the miR-150-5p/MCL1 axis. These findings indicated that HULC enhanced imatinib resistance in CML by modulating the miR-150-5p/MCL1 axis, providing a promising biomarker for CML.
慢性髓系白血病（CML）是一种骨髓增生性肿瘤。异常表达的长链非编码 RNA 肝癌高上调（HULC）已被牵连在肿瘤进展，包括 CML。本研究旨在探讨 HULC 在 CML 中的作用。通过定量实时 PCR 或 Western blot 检测 HULC、miR-150-5p 和髓样细胞白血病 1（MCL1）的水平。细胞计数试剂盒-8 检测细胞活力和半抑制浓度。通过流式细胞术和 Western blot 监测细胞凋亡。通过双荧光素酶报告基因检测验证 HULC、miR-150-5p 和 MCL1 之间的相互作用。使用 Western blot 检测磷脂酰肌醇 3-激酶（PI3K）、蛋白激酶 B（AKT）和磷酸化-AKT 的表达。CML 患者和 CML 细胞的骨髓单个核细胞中 HULC 和 MCL1 上调，而 miR-150-5p 下调。HULC 过表达增加 K562 细胞对伊马替尼的耐药性，HULC 耗竭增强伊马替尼耐药细胞（K562-R）对伊马替尼的敏感性。机制上，HULC 是 miR-150-5p 的海绵。HULC 通过调节 miR-150-5p 促进伊马替尼耐药。MCL1 与 miR-150-5p 结合并逆转 HULC 对伊马替尼耐药的影响。HULC 通过 miR-150-5p/MCL1 轴调节 PI3K/AKT 通路。这些发现表明，HULC 通过调节 miR-150-5p/MCL1 轴增强 CML 对伊马替尼的耐药性，为 CML 提供了有前途的生物标志物。
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