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Inhibition of miR-21 induces biological and behavioral alterations in diffuse large B-cell lymphoma

机译:抑制miR-21可诱导弥漫性大B细胞淋巴瘤的生物学和行为改变

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摘要

MicroRNA-21 (miR-21) has been ascribed a key role in many cellular processes, e.g. tumorigenesis via inhibition of target gene expression. However, its role in diffuse large B-cell lymphoma (DLBCL) is still unclear, and there are no in-depth studies on the relationship between miR-21 and the cellular phenotype of DLBCL. In this study, we investigated the expression and role of miR-21 in the regulation of cell biological processes in DLBCL. Firstly, miR-21 expression was evaluated in three DLBCL cell lines by real-time quantitative reverse-transcription (qRT) polymerase chain reaction (PCR). Then, to determine the possible role of miR-21 in the biological and behavioral characteristics of DLBCL, we performed miR-21 knockdown by transfection with anti-miR-21. In addition, PDCD4 and PTEN were assessed by luciferase reporter assay, qRT-PCR, and Western blot. Our study revealed that miR-21 was significantly upregulated in activated B-cell-like DLBCL cells compared to germinal center-like DLBCL cells. We demonstrated that inhibition of miR-21 induced suppression of proliferation and invasion, as well as increased apoptosis in DLBCL. Moreover, knockdown of miR-21 increased PDCD4 and PTEN expression at the protein level but not at the mRNA level. In conclusion, miR-21 can regulate proliferation, invasion, and apoptosis, and thus it has a potential therapeutic application in DLBCL.
机译:MicroRNA-21(miR-21)被认为在许多细胞过程中起着关键作用,例如通过抑制靶基因表达实现肿瘤发生。但是,其在弥漫性大B细胞淋巴瘤(DLBCL)中的作用尚不清楚,并且还没有深入研究miR-21与DLBCL细胞表型之间的关系。在这项研究中,我们调查了miR-21在DLBCL中调节细胞生物学过程的表达及其作用。首先,通过实时定量逆转录(qRT)聚合酶链反应(PCR)评价了三种DLBCL细胞系中的miR-21表达。然后,为了确定miR-21在DLBCL的生物学和行为特征中的可能作用,我们通过用抗miR-21转染进行了miR-21敲低。另外,通过荧光素酶报告基因测定,qRT-PCR和Western印迹评估PDCD4和PTEN。我们的研究表明,与生发中心样DLBCL细胞相比,miR-21在活化的B细胞样DLBCL细胞中显着上调。我们证明了抑制miR-21会诱导增殖和侵袭抑制,以及DLBCL中凋亡的增加。此外,敲低miR-21可以在蛋白质水平上增加PDCD4和PTEN表达,而在mRNA水平上则没有。总之,miR-21可以调节增殖,侵袭和凋亡,因此在DLBCL中具有潜在的治疗应用。

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