ARAP1-AS1 Overexpression Increases Diffuse Large B Cell Lymphoma Progression by Sponging miR-508–5p to Activate the EMP1-PI3K/AKT Pathway

IF 3.9 4区 医学 Q2 HEMATOLOGY Hematological Oncology Pub Date : 2025-04-14 DOI:10.1002/hon.70056
Yamei Chen, Minmin Ren, Lei Zhu, Ting Sun, Xiaoyong Wang, Lingling Jiang, Linlin Zhou, Dongyun Gao
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Abstract

Diffuse large B cell lymphoma (DLBCL) is a type of common and fatal non-Hodgkin lymphoma. This study aimed to detect the specific function of lncRNA ARAP1-AS1 in DLBCL. The in vitro experiments were performed using RT-qPCR, western blotting, MTT, colony formation, flow cytometry analysis, FISH, RNA pulldown, and luciferase reporter assays. A xenograft mouse model was used to evaluate tumor growth in vivo. ARAP1-AS1 expression was upregulated in DLBCL tissues and cells. ARAP1-AS1 knockdown inhibited DLBCL cell proliferation and promoted apoptosis. ARAP1-AS1 activated PI3K/AKT signaling by upregulating EMP1 expression via miR-508–5p. EMP1 overexpression markedly abolished the effect of ARAP1-AS1 knockdown on DLBCL cell proliferation and apoptosis, and PI3K inhibitor reversed the effect of ARAP1-AS1 overexpression on DLBCL cells. ARAP1-AS1 knockdown inhibited DLBCL tumor growth and reduced Ki-67, EMP1, and p-AKT expression in xenograft mouse models. ARAP1-AS1 knockdown exerts anti-tumor effect on DLBCL progression through the miR-508–5p/EMP1/PI3K/AKT axis.

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ARAP1-AS1过表达通过抑制miR-508-5p激活EMP1-PI3K/AKT通路增加弥漫性大B细胞淋巴瘤进展
弥漫性大B细胞淋巴瘤(DLBCL)是一种常见的致死性非霍奇金淋巴瘤。本研究旨在检测lncRNA ARAP1-AS1在DLBCL中的具体功能。体外实验采用RT-qPCR、western blotting、MTT、集落形成、流式细胞术分析、FISH、RNA pull - down和荧光素酶报告基因检测进行。采用异种移植小鼠模型评价肿瘤在体内的生长情况。ARAP1-AS1在DLBCL组织和细胞中表达上调。敲低ARAP1-AS1抑制DLBCL细胞增殖,促进细胞凋亡。ARAP1-AS1通过miR-508-5p上调EMP1表达激活PI3K/AKT信号通路。EMP1过表达可明显消除ARAP1-AS1敲低对DLBCL细胞增殖和凋亡的影响,PI3K抑制剂可逆转ARAP1-AS1过表达对DLBCL细胞的影响。在异种移植小鼠模型中,ARAP1-AS1敲低抑制DLBCL肿瘤生长,降低Ki-67、EMP1和p-AKT的表达。ARAP1-AS1敲低通过miR-508-5p /EMP1/PI3K/AKT轴对DLBCL进展发挥抗肿瘤作用。
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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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