Department of Hematology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan City People's Hospital, Jinan, China.
Department of Hematology, Qingdao Binhai University Affiliated Hospital, Qingdao, China.
Leuk Lymphoma. 2021 Feb;62(2):428-437. doi: 10.1080/10428194.2020.1832667. Epub 2020 Oct 15.
A growing body of evidence indicates that long non-coding RNA (lncRNA) is involved in the development and progression of many diseases. It has been reported that lncRNA LINC00467 is disregulated in multiple tumors, while its role in acute myeloid leukemia (AML) is still unknown. Here, we find that LINC00467 expression is significantly increased in AML specimens and cell lines. Further investigations show that knockdown of LINC00467 inhibits the malignant phenotypes of AML cells. Consistently, LINC00467 knockdown slows AML progression in immunodeficient mice. Interestingly, microRNA-339 (miR-339) is upregulated and its target gene SKI, an oncogene, is downregulated in AML cells after LINC00467 knockdown. More importantly, inhibition of miR-339 can largely abolish the effect of LINC00467 knockdown on AML cells. Collectively, our data demonstrate that LINC00467 plays an important role in the pathogenesis of AML by targeting the miR-339/SKI pathway, which provides a new sight for the subsequent treatment of AML.
越来越多的证据表明,长非编码 RNA(lncRNA)参与许多疾病的发生和发展。据报道,lncRNA LINC00467 在多种肿瘤中失调,但其在急性髓系白血病(AML)中的作用尚不清楚。在这里,我们发现 LINC00467 的表达在 AML 标本和细胞系中显著增加。进一步的研究表明,LINC00467 的敲低抑制了 AML 细胞的恶性表型。一致地,LINC00467 的敲低在免疫缺陷小鼠中减缓了 AML 的进展。有趣的是,在 LINC00467 敲低后,miR-339(miR-339)上调,其靶基因 SKI(一种癌基因)下调。更重要的是,抑制 miR-339 可以在很大程度上消除 LINC00467 敲低对 AML 细胞的影响。总之,我们的数据表明,LINC00467 通过靶向 miR-339/SKI 通路在 AML 的发病机制中发挥重要作用,为随后的 AML 治疗提供了新的视角。