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miR-218-5p 通过 LRIG1 促进乳腺癌的恶性行为。

MicroRNA-218-5p accelerates malignant behaviors of breast cancer through LRIG1.

机构信息

School of Medicine, Tongji University, China.

Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, China.

出版信息

Clinics (Sao Paulo). 2023 Oct 28;78:100302. doi: 10.1016/j.clinsp.2023.100302. eCollection 2024.

Abstract

OBJECTIVE

MicroRNAs play crucial roles in the pathogenesis of cancers. MiRNA-218-5p may act as either an oncogene or a tumor suppressor, but its role in the pathogenesis of Breast Cancer (BC) remains unclear.

METHODS

Infiltrative breast ductal carcinoma as well as corresponding adjacent normal samples were collected from 30 patients. Mimics and inhibitors of miRNA-218-5p or corresponding negative controls were transfected into BC cells. miRNA-218-5p expression was detected by quantitative PCR. The effects of miRNA-218-5p on the malignant behaviors of BC were assessed. Dual-luciferase reporter assay was employed to evaluate the binding of miRNA-218-5p to LRIG1.

RESULTS

BC tissues showed higher miRNA-218-5p expression as compared to the adjacent normal tissues. Ectopic miRNA-218-5p expression accelerated the cell cycle, cell growth and migration of BC, while repressed cell apoptosis. Interestingly, ectopic miRNA-218-5p expression down-regulated LRIG1 expression, and miRNA-218-5p could bind to LRIG1. Also, our study indicated that miRNA-218-5p up-regulated ErbB2 and EGFR expression by targeting LRIG1, suggesting that the LRIG1-mediated signaling pathway contributed to the pro-tumor effects of miRNA-218-5p on BC.

CONCLUSION

MiRNA-218-5p up-regulates ErbB2 and EGFR expression by suppressing LRIG1 expression, thus promoting the malignant behaviors of BC. miRNA-218-5p may exert a pro-tumor effect on BC and serve as a therapeutic target for BC treatment.

摘要

目的

microRNAs 在癌症的发病机制中发挥着关键作用。miRNA-218-5p 可能作为癌基因或肿瘤抑制因子发挥作用,但它在乳腺癌(BC)发病机制中的作用尚不清楚。

方法

收集 30 例浸润性乳腺导管癌及相应的相邻正常组织。将 miRNA-218-5p 的模拟物和抑制剂或相应的阴性对照转染到 BC 细胞中。采用定量 PCR 检测 miRNA-218-5p 的表达。评估 miRNA-218-5p 对 BC 恶性行为的影响。采用双荧光素酶报告基因检测评估 miRNA-218-5p 与 LRIG1 的结合。

结果

与相邻正常组织相比,BC 组织中 miRNA-218-5p 的表达水平更高。外源性 miRNA-218-5p 表达加速了 BC 细胞周期、细胞生长和迁移,同时抑制了细胞凋亡。有趣的是,外源性 miRNA-218-5p 表达下调了 LRIG1 的表达,miRNA-218-5p 可以与 LRIG1 结合。此外,我们的研究表明,miRNA-218-5p 通过靶向 LRIG1 下调 ErbB2 和 EGFR 的表达,提示 LRIG1 介导的信号通路有助于 miRNA-218-5p 对 BC 的促肿瘤作用。

结论

miRNA-218-5p 通过抑制 LRIG1 的表达而上调 ErbB2 和 EGFR 的表达,从而促进 BC 的恶性行为。miRNA-218-5p 可能对 BC 发挥促肿瘤作用,并可作为 BC 治疗的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bad/10632409/2055728d5539/gr1.jpg

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