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miR-4319 通过抑制 CD147 介导的 MMPs 表达抑制视网膜母细胞瘤细胞的增殖、迁移、侵袭和 EMT 进展。

miR-4319 inhibited retinoblastoma cells proliferation, migration, invasion and EMT progress via suppressing CD147 mediated MMPs expression.

机构信息

Department of Ophthalmology, Xi'an Children's Hospital, No. 69, Xijuyuan Road, Lianhu District, Xi'an, 710003, China.

Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, 100069, China.

出版信息

J Mol Histol. 2021 Apr;52(2):269-277. doi: 10.1007/s10735-020-09946-w. Epub 2021 Jan 20.

Abstract

Tumor migration is the critical step that lead to the migration in retinoblastoma (RB), in which microRNAs (miRNAs) play important roles. This study aimed to investigate the role of microRNA-4319 (miR-4319) in the development of retinoblastoma by identifying its targets, as well as its underlying regulatory mechanisms. Our data shown that miR-4319 was downregulated in RB tissues and RB cell lines. Enhanced miR-4319 suppressed cell proliferation, migration, invasion and EMT progress, promoted cell apoptosis in SO-RB50 and RB-Y79 cells. Of note, extracellular matrix metalloproteinase inducer (EMMPRI/CD147) was identified as a direct target gene for miR-4319. MMPs were regulated by CD147 and participated in the miR-4319 regulatory network in SO-RB50 cells. In addition, overexpression of CD147 abrogated the inhibitory effect of miR-4319 on RB cells. In summary, miR-4319 overexpression suppressed cell proliferation, migration and invasion may through suppressing the CD147 mediated MMPs expression, suggesting that miR-4319 may serve as a potential diagnostic biomarker and treatment target for RB.

摘要

肿瘤迁移是导致视网膜母细胞瘤(RB)转移的关键步骤,其中 microRNAs(miRNAs)发挥着重要作用。本研究旨在通过鉴定其靶标以及潜在的调控机制,研究 microRNA-4319(miR-4319)在视网膜母细胞瘤发生发展中的作用。我们的数据表明,miR-4319 在 RB 组织和 RB 细胞系中下调。增强 miR-4319 抑制 SO-RB50 和 RB-Y79 细胞的增殖、迁移、侵袭和 EMT 进展,促进细胞凋亡。值得注意的是,细胞外基质金属蛋白酶诱导因子(EMMPRI/CD147)被鉴定为 miR-4319 的直接靶基因。MMPs 受 CD147 调控,并参与 SO-RB50 细胞中的 miR-4319 调控网络。此外,CD147 的过表达消除了 miR-4319 对 RB 细胞的抑制作用。总之,miR-4319 的过表达抑制细胞增殖、迁移和侵袭可能是通过抑制 CD147 介导的 MMPs 表达实现的,提示 miR-4319 可能作为 RB 的潜在诊断生物标志物和治疗靶点。

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