上调miR-29a-3p通过靶向MCL1阻止淋巴瘤细胞的恶性特征

IF 3.9 4区 医学 Q2 HEMATOLOGY
Tengfei Shi, Xiali Wu, Aichun Liu
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引用次数: 0

摘要

弥漫性大b细胞淋巴瘤(DLBCL)是最常见的成人淋巴瘤,临床表现为侵袭性,进展迅速。越来越多的证据表明,microRNAs (miRNAs)参与了各种人类肿瘤的发病机制。研究miR-29a-3p的表达及其机制可能为DLBCL的发病和监测提供新的治疗靶点。采用PCR反应检测大细胞淋巴瘤组织、血清和细胞样本中miR-29a-3p的表达水平。ROC曲线反映miR-29a-3p对DLBCL患者的筛查能力。通过双荧光素酶活性测定验证miR-29a-3p的靶点。转染检测上调miR-29a-3p和MCL1的表达,随后使用CCK-8、Transwell检测和流式细胞术进行功能表征。miR-29a-3p在DLBCL中下调,具有鉴别DLBCL患者的高潜力。MCL1是一个经过验证的miR-29a-3p靶点,在DLBCL中显著表达。miR-29a-3p模拟物显著抑制DLBCL细胞活性和不良行为,部分被MCL1过表达抵消。高水平的miR-29a-3p靶向MCL1以阻止DLBCL细胞的恶性行为,这表明miR-29a-3p/MCL1轴可能是DLBCL的候选治疗和监测标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Upregulated miR-29a-3p Prevent Malignant Features of Lymphoma Cells by Targeting MCL1

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent adult lymphoma, which exhibits aggressive clinical behavior with rapid progression. Accumulating evidence implicates microRNAs (miRNAs) in the pathogenesis of various human tumors. Investigating miR-29a-3p expression and mechanism may reveal novel therapeutic targets for DLBCL pathogenesis and monitoring. The levels of miR-29a-3p in DLBCL tissue, serum and cell samples were determined by PCR reactions. ROC curve reflected the screening ability of miR-29a-3p for DLBCL patients. The target of miR-29a-3p was verified by dual-luciferase activity assay. Transfection assays were employed to upregulate miR-29a-3p and MCL1 expression, followed by functional characterization using CCK-8, Transwell assays and flow cytometry. miR-29a-3p is downregulated in DLBCL, which has a high potential to identify DLBCL patients. MCL1 is a validated miR-29a-3p target prominently expressed in DLBCL. miR-29a-3p mimic notably suppressed DLBCL cell activity and adverse behavior, which was partially counteracted by MCL1 overexpression. High levels of miR-29a-3p target MCL1 to prevent DLBCL cell malignant behavior, highlighting that miR-29a-3p/MCL1 axis may be a candidate therapeutic and monitoring marker for DLBCL.

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来源期刊
Hematological Oncology
Hematological Oncology 医学-血液学
CiteScore
4.20
自引率
6.10%
发文量
147
审稿时长
>12 weeks
期刊介绍: Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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