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miR-182-5p 通过调控 BCL2L12 和 BCL2 的表达在急性髓系白血病中发挥作用,有望成为一个治疗靶点。

MiR-182-5p regulates BCL2L12 and BCL2 expression in acute myeloid leukemia as a potential therapeutic target.

机构信息

Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China; Department of Clinical Laboratory Medicine, Shantou Central Hospital, Guangdong, China.

Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.

出版信息

Biomed Pharmacother. 2018 Jan;97:1189-1194. doi: 10.1016/j.biopha.2017.11.002. Epub 2017 Nov 11.

Abstract

The importance of microRNAs (miRNAs) are shown during various cancers including acute myeloid leukemia (AML). MiR-182-5p functions as an oncogene or a potential suppressive miRNA in cancers, but its expression and function in AML is unknown. The purpose is to investigate the roles of miR-182-5p in AML in this study. MiR-182-5p was examined in the blood samples of AML and it was found that miR-182-5p expression levels were higher in AML tissues than it in their normal controls, so did in the AML cells. BCL2L12 and BCL2 were predicted as target genes of miR-182-5p and verified using luciferase reporter assay. BCL2L12 and BCL2 mRNA and protein levels were up-regulated in the AML cells with miR-182-5p inhibition. Cellular function of miR-182-5p indicated that miR-182-5p suppression in AML cells could decrease cell proliferation and reverse cisplatin (DDP) resistance via targeting BCL2L12 and BCL2 expression. Inhibition of miR-182-5p promoted AML cell apoptosis by targeting BCL2 or BCL2L12. The study demonstrates that high levels of miR-182-5p in AML promotes cell proliferation and suppresses cell apoptosis by targeting BCL2L12 and BCL2.

摘要

miRNAs(miRNA)在各种癌症中都具有重要作用,包括急性髓系白血病(AML)。miR-182-5p 在癌症中作为癌基因或潜在的抑制性 miRNA 发挥作用,但它在 AML 中的表达和功能尚不清楚。本研究旨在探讨 miR-182-5p 在 AML 中的作用。在 AML 的血液样本中检测到 miR-182-5p,发现其在 AML 组织中的表达水平高于正常对照,AML 细胞中也是如此。BCL2L12 和 BCL2 被预测为 miR-182-5p 的靶基因,并通过荧光素酶报告基因实验进行验证。miR-182-5p 抑制后,AML 细胞中的 BCL2L12 和 BCL2 mRNA 和蛋白水平上调。miR-182-5p 在 AML 细胞中的功能表明,通过靶向 BCL2L12 和 BCL2 表达,抑制 miR-182-5p 可降低细胞增殖并逆转顺铂(DDP)耐药性。抑制 miR-182-5p 通过靶向 BCL2 或 BCL2L12 促进 AML 细胞凋亡。该研究表明,AML 中高水平的 miR-182-5p 通过靶向 BCL2L12 和 BCL2 促进细胞增殖并抑制细胞凋亡。

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