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反义寡核苷酸靶向 miR-21 抑制白血病 K562 细胞迁移并诱导其凋亡。

Antisense oligonucleotide against miR-21 inhibits migration and induces apoptosis in leukemic K562 cells.

机构信息

Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.

出版信息

Leuk Lymphoma. 2010 Apr;51(4):694-701. doi: 10.3109/10428191003596835.

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that are widely involved in cancer-related processes. The microRNA-21 (miR-21) has been identified as the only miRNA overexpressed in a variety of cancers, including leukemia. However, the function of miR-21 is yet unknown in chronic myelogenous leukemia (CML). Antisense oligonucleotides (ASOs), as inhibitors of miRNAs, have already been applied to therapeutic development and functional identification in miRNA research. In this study, we found that the antisense inhibition of miR-21 in K562 cells suppressed cell migration, promoted cell apoptosis, and inhibited cell growth, and up-regulated the expression of the tumor suppressor gene PDCD4. Meanwhile, pre-miRNA-21 increased migration and decreased cell apoptosis without affecting proliferation. We also validated that PDCD4 is a functional target of miR-21 in K562 cells. These effects of miR-21 might be partially due to its regulation of PDCD4. Our data suggest that miR-21 may play an oncogenic role in the cellular processes of CML, and antisense inhibition of miR-21 may therefore be useful as CML therapy.

摘要

微小 RNA(miRNAs)是一种广泛参与癌症相关过程的小型非编码 RNA 分子。miR-21 已被确定为多种癌症(包括白血病)中唯一过度表达的 miRNA。然而,miR-21 在慢性髓性白血病(CML)中的功能尚不清楚。反义寡核苷酸(ASO)作为 miRNA 的抑制剂,已被应用于 miRNA 研究中的治疗开发和功能鉴定。在这项研究中,我们发现 miR-21 在 K562 细胞中的反义抑制抑制了细胞迁移,促进了细胞凋亡,抑制了细胞生长,并上调了肿瘤抑制基因 PDCD4 的表达。同时,pre-miRNA-21 增加了迁移,减少了细胞凋亡,而不影响增殖。我们还验证了 PDCD4 是 K562 细胞中 miR-21 的功能靶点。miR-21 的这些作用可能部分归因于其对 PDCD4 的调节。我们的数据表明,miR-21 可能在 CML 的细胞过程中发挥致癌作用,因此反义抑制 miR-21 可能对 CML 治疗有用。

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