Abstract

Background

Increasing evidence has shown that the dysregulation of miRNAs is involved in the pathogenesis of retinoblastoma (RB). This present study was aimed to investigate the significance of miR-375 in RB progression, and the underlying mechanism.

Materials and methods

The miR-375 expression was detected by RT-PCR. CCK-8 assay and transwell assays were used to measure RB cell viability, migration, and invasion. The downstream gene of miR-375 was verified by luciferase reporter assay. Western blot was applied to detect the related proteins of MAPK1/MAPK3 signalling pathway.

Results

MiR-375 was decreased significantly in RB tissues, and its down-regulation was associated with the poor prognosis of RB patients. Over-expression of miR-375 inhibited RB cell proliferation, migration, and invasion. More importantly, miR-375 modulated ERBB2 expression negatively, and ERBB2 was confirmed as the target of miR-375. Moreover, ERBB2 overturned the inhibitory effect of miR-375 mimic on the progression of RB. MiR-375 mimic suppressed RB progression via inhibiting the activation of MAPK1/MAPK3 signalling pathway.

Conclusions

MiR-375 inhibited RB progression through targeting ERBB2 and suppressing MAPK1/MAPK3 signalling pathway, which might be a new target for the clinical treatment strategy.

中文翻译：

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MiRNA-375通过靶向ERBB2和抑制MAPK1/MAPK3信号通路抑制视网膜母细胞瘤进展

摘要

背景

越来越多的证据表明，miRNA 的失调与视网膜母细胞瘤 (RB) 的发病机制有关。本研究旨在探讨 miR-375 在 RB 进展中的意义及其潜在机制。

材料和方法

通过RT-PCR检测miR-375的表达。CCK-8 测定和 transwell 测定用于测量 RB 细胞活力、迁移和侵袭。miR-375的下游基因通过萤光素酶报告基因检测验证。应用Western blot检测MAPK1/MAPK3信号通路相关蛋白。

结果

MiR-375在RB组织中显着降低，其下调与RB患者预后不良有关。miR-375的过表达抑制RB细胞增殖、迁移和侵袭。更重要的是，miR-375负向调节ERBB2表达，ERBB2被证实是miR-375的靶点。此外，ERBB2 推翻了 miR-375 模拟物对 RB 进展的抑制作用。MiR-375 模拟物通过抑制 MAPK1/MAPK3 信号通路的激活来抑制 RB 进展。

结论

MiR-375通过靶向ERBB2和抑制MAPK1/MAPK3信号通路抑制RB进展，这可能是临床治疗策略的新靶点。