Department of Hematology, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
Department of Hematology, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):1-8. doi: 10.1016/j.bbrc.2018.09.034. Epub 2018 Oct 23.
Chronic myeloid leukemia (CML) is a type of cancer that starts in certain blood-forming cells of the bone marrow. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well known protooncogene, has be shown to be upregulated in various tumor types, including multiple myeloma. However, the biological function of MALAT1 in CML remains has yet to be explored. This study was designed to investigate the effects of MALAT1 on the physiological processes in CML and its underlying mechanisms, which will be helpful for us to have a better understanding of CML development and progression as well as improved therapeutic method.
Recombinant virus construction and infection was performed to overexpress or knockdown the expression of MALAT1. Dual luciferase reporter assay was applied to vetify the interaction between MALAT1 and miR-328. The cell viability and cell cycle were analyzed by CCK-8 assay and flow cytometry, respectively. Quantitative real time PCR and western blotting assays were used to measure the expression of genes and proteins.
The expression of MALAT1 was significantly increased in CML cells compared with peripheral blood cells from health donors. Silencing of MALAT1 significantly inhibited the proliferation and arrested cell cycle of CML cells by targeting miR-328. Moreover, MALAT1 knockdown enhanced imatinib sensitivity of K562 cells, while silencing of miR-328 abolished this effect.
These findings indicate that lncRNA MALAT1/miR-328 axis promotes the proliferation and imatinib resistance of CML cells, providing new perspectives for the future study of MALAT1 as a therapeutic target for CML.
慢性髓细胞白血病（CML）是一种起源于骨髓中某些造血细胞的癌症。长链非编码 RNA 转移相关肺腺癌转录本 1（MALAT1）是一种已知的原癌基因，已被证明在多种肿瘤类型中上调，包括多发性骨髓瘤。然而，MALAT1 在 CML 中的生物学功能尚未得到探索。本研究旨在探讨 MALAT1 对 CML 生理过程的影响及其潜在机制，这将有助于我们更好地理解 CML 的发展和进展，并改善治疗方法。
通过重组病毒构建和感染过表达或敲低 MALAT1 的表达。应用双荧光素酶报告基因实验验证 MALAT1 和 miR-328 之间的相互作用。通过 CCK-8 assay 和流式细胞术分别分析细胞活力和细胞周期。通过定量实时 PCR 和 Western blot assay 检测基因和蛋白的表达。
与健康供者外周血细胞相比，CML 细胞中 MALAT1 的表达明显增加。沉默 MALAT1 通过靶向 miR-328 显著抑制 CML 细胞的增殖并阻滞细胞周期。此外，MALAT1 敲低增强了 K562 细胞对伊马替尼的敏感性，而 miR-328 的沉默则消除了这种效应。
这些发现表明，lncRNA MALAT1/miR-328 轴促进了 CML 细胞的增殖和伊马替尼耐药性，为未来将 MALAT1 作为 CML 的治疗靶点提供了新的视角。
