Second Clinical College, Tongji Medical College, Huazhong University of Science and TechnologyWuhanP. R. China.
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanP. R. China.
Oncol Res. 2020 Sep 1;28(4):357-369. doi: 10.3727/096504020X15844389264424. Epub 2020 Mar 17.
It has been reported that kindlin-3 expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and precise mechanisms of kindlin-3 in acute myeloid leukemia (AML) have not been well clarified. Our study aimed to explore the interaction between kindlin-3 and miR-4792 in AML. In our study, we found that the expression of kindlin-3 was dramatically increased in AML samples and cell lines, and the miR-4792 level was significantly downregulated. Interestingly, the low miR-4792 level was closely associated with upregulated kindlin-3 expression in AML samples. Moreover, introduction of miR-4792 dramatically suppressed proliferation and invasion and induced apoptosis of AML cells. We demonstrated that miR-4792 could directly target kindlin-3 by using both bioinformatics analysis and luciferase reporter assay. In addition, kindlin-3 silencing had similar effects with miR-4792 overexpression on AML cells. Overexpression of kindlin-3 in AML cells partially reversed the inhibitory effects of miR-4792 mimic. miR-4792 inhibited cell proliferation and invasion and induced apoptosis of AML cells by directly downregulating kindlin-3 expression, and miR-4792 targeting kindlin-3 was responsible for the regulation of the proliferation, invasion, and apoptosis of AML cells.
已有报道称，连接蛋白-3（kindlin-3）的表达与许多癌症的进展和 microRNA（miRNA）加工密切相关。然而，kindlin-3 在急性髓系白血病（AML）中的作用及其确切机制尚不清楚。本研究旨在探讨 kindlin-3 与 miR-4792 在 AML 中的相互作用。在本研究中，我们发现 kindlin-3 的表达在 AML 样本和细胞系中显著增加，而 miR-4792 的水平显著下调。有趣的是，miR-4792 水平较低与 AML 样本中上调的 kindlin-3 表达密切相关。此外，miR-4792 的引入可显著抑制 AML 细胞的增殖、侵袭并诱导其凋亡。我们通过生物信息学分析和荧光素酶报告基因检测证实，miR-4792 可直接靶向 kindlin-3。此外，沉默 kindlin-3 可产生与 miR-4792 过表达类似的 AML 细胞效应。AML 细胞中 kindlin-3 的过表达部分逆转了 miR-4792 模拟物的抑制作用。miR-4792 通过直接下调 kindlin-3 的表达抑制 AML 细胞的增殖和侵袭并诱导其凋亡，而 miR-4792 靶向 kindlin-3 负责调节 AML 细胞的增殖、侵袭和凋亡。
