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miR-17-3p 通过抑制 LMLN 下调 P21 表达促进多发性骨髓瘤细胞增殖。

miR-17-3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition.

机构信息

Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Hematology Institute, Zhengzhou, Henan, China.

China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.

出版信息

Int J Cancer. 2021 Jun 15;148(12):3071-3085. doi: 10.1002/ijc.33528. Epub 2021 Mar 1.

Abstract

Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR-17-3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR-17-3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR-17-3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR-17-3p might be a diagnostic index of MM. Moreover, miR-17-3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR-17-3p. Negatively regulated by miR-17-3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR-17-3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR-17-3p-LMLN-P21 axis in MM progression.

摘要

多发性骨髓瘤(MM)是一种血液恶性肿瘤,预后较差,需要进行侵入性操作。有报道称 miRNA 与血液恶性肿瘤的诊断、治疗和预后有关。在本研究中,我们评估了 miR-17-3p 在多发性骨髓瘤患者血浆和骨髓单个核细胞中的表达谱,并与单克隆丙种球蛋白病(MGUS)患者和健康对照者进行了比较。结果表明,MM 患者血浆和单个核细胞中 miR-17-3p 的表达水平高于 MGUS 患者和正常对照组。此外,miR-17-3p 的表达与诊断指标呈正相关,如骨髓浆细胞丰富度和血清 M 蛋白水平,与疾病的国际分期系统(ISS)分期呈正相关。受试者工作特征曲线分析表明,miR-17-3p 可能是 MM 的诊断指标。此外,miR-17-3p 通过 P21 调节 MM 细胞系中的细胞增殖、凋亡和细胞周期,并在体内促进 MM 肿瘤生长。此外,我们预测并验证了 LMLN 是 miR-17-3p 的功能性下游靶基因。miR-17-3p 负调控 LMLN,通过 P21 抑制 MM 细胞生长,发挥肿瘤抑制功能。综上所述,我们的数据表明 miR-17-3p 可作为 MM 临床诊断的有前途的生物标志物,并揭示了 MM 进展中的新的 miR-17-3p-LMLN-P21 轴。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01b/8248421/3255e06f78bf/IJC-148-3071-g005.jpg

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