Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, China.
The Center for Clinical Molecular Medical Detection, the First Affiliated Hospital of Chongqing Medical University, China.
FEBS Open Bio. 2021 Feb;11(2):519-528. doi: 10.1002/2211-5463.13063. Epub 2020 Dec 30.
Multiple myeloma (MM) is a heterogeneous disease with poor prognosis. Increasing evidence has revealed that microRNAs (miRNAs) are strongly associated with the pathogenesis and progression of MM. Here, we investigated the role of microRNA-637 (miR-637) in MM to identify potential therapeutic targets. We measured the expression of miR-637 in bone marrow samples of MM patients and MM cell lines by quantitative real-time PCR and western blot. The effect of miR-637 on proliferation and apoptosis of MM primary cells was also investigated. Analyses of four bioinformatics databases showed that miR-637 is associated with nuclear protein 1 (NUPR1) in MM cells, which was confirmed by luciferase reporter assay. We found that the overexpression of miR-637 suppressed the development of MM. miR-637 mimics increased the levels of Bax, cleaved caspase 3, and P62, and decreased the levels of Bcl2 and LC3. Additionally, luciferase reporter assays were performed to demonstrate that NUPR1 is the main target of miR-637 in MM cells. Overexpression of NUPR1 reversed the effects of miR-637 mimics in MM cells. Our results suggest that miR-637 inhibits cell proliferation and autophagy, and promotes apoptosis in MM cells by targeting NUPR1. Our findings also suggest that miR-637 may have potential as a novel molecular therapeutic target for MM treatment.
多发性骨髓瘤（MM）是一种预后不良的异质性疾病。越来越多的证据表明，microRNAs（miRNAs）与 MM 的发病机制和进展密切相关。在这里，我们研究了 microRNA-637（miR-637）在 MM 中的作用，以确定潜在的治疗靶点。我们通过定量实时 PCR 和 Western blot 测量了 MM 患者和 MM 细胞系中 miR-637 的表达。还研究了 miR-637 对 MM 原代细胞增殖和凋亡的影响。四个生物信息学数据库的分析表明，miR-637 与 MM 细胞中的核蛋白 1（NUPR1）有关，这通过荧光素酶报告基因检测得到了证实。我们发现，miR-637 的过表达抑制了 MM 的发展。miR-637 模拟物增加了 Bax、cleaved caspase 3 和 P62 的水平，并降低了 Bcl2 和 LC3 的水平。此外，进行了荧光素酶报告基因检测，以证明 NUPR1 是 MM 细胞中 miR-637 的主要靶标。NUPR1 的过表达逆转了 miR-637 模拟物在 MM 细胞中的作用。我们的结果表明，miR-637 通过靶向 NUPR1 抑制 MM 细胞的增殖和自噬，并促进凋亡。我们的研究结果还表明，miR-637 可能成为 MM 治疗的一种新的分子治疗靶点。
