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miR-106b-5p 通过靶向 CNN1 并调节 Rho/ROCK1 通路促进乳腺癌肺转移。

miR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway.

机构信息

Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Cancer Metastasis Institute, Fudan University, Shanghai 200040, China.

出版信息

Aging (Albany NY). 2020 Jan 27;12(2):1867-1887. doi: 10.18632/aging.102719.

Abstract

OBJECTIVES

Breast cancer has been the second most prevalent and fatal malignancy due to its frequent metastasis to other organs. We aim to study the effects of a key miRNA-mRNA signaling in breast cancer.

RESULTS

CNN1 was identified as the key gene in breast cancer by the bioinformatics analysis, and the downregulation of CNN1 in breast cancer tissues and cell lines was observed. Upregulating CNN1 inhibited cell survival, migration, invasion, and adhesion, but enhanced cell apoptosis. miR-106b-5p not only bound to CNN1 mRNA 3'UTR, but also promoted lung metastasis . Besides, the miR-106b-5p mimic enhanced breast cancer canceration by targeting CNN1 and activating Rho/ROCK1 signaling pathway.

CONCLUSION

Overall, our results proved that miR-106b-5p promoted the metastasis of breast cancer by suppressing CNN1 and activating Rho/ROCK1 pathway.

METHODS

Bioinformatics analysis was performed to select the key gene in breast cancer. The overexpression and knockdown of Calponin 1 (CNN1) in breast cancer cell lines were performed to conduct cell viability, migrating, invasion, proliferation, adhesion, and apoptosis experiments. To identify the role of miR-106b-5p and Rho/ROCK1 in CNN1-induced breast cancer, a dual-luciferase assay, tumor lung metastasis assay, transcript half-life assay, and Rho/ROCK1 inhibition assay were performed.

摘要

目的

由于乳腺癌经常转移到其他器官,因此已成为第二大常见和致命的恶性肿瘤。我们旨在研究关键 miRNA-mRNA 信号在乳腺癌中的作用。

结果

通过生物信息学分析鉴定出 CNN1 是乳腺癌的关键基因,并观察到 CNN1 在乳腺癌组织和细胞系中的下调。上调 CNN1 抑制细胞存活、迁移、侵袭和黏附,但促进细胞凋亡。miR-106b-5p 不仅与 CNN1 mRNA 3'UTR 结合,而且还促进肺转移。此外,miR-106b-5p 模拟物通过靶向 CNN1 并激活 Rho/ROCK1 信号通路增强乳腺癌的癌变。

结论

总之,我们的结果证明 miR-106b-5p 通过抑制 CNN1 和激活 Rho/ROCK1 通路促进乳腺癌的转移。

方法

进行生物信息学分析以选择乳腺癌中的关键基因。在乳腺癌细胞系中过表达和敲低 Calponin 1 (CNN1) 以进行细胞活力、迁移、侵袭、增殖、黏附和凋亡实验。为了确定 miR-106b-5p 和 Rho/ROCK1 在 CNN1 诱导的乳腺癌中的作用,进行了双荧光素酶报告基因检测、肿瘤肺转移检测、转录半衰期检测和 Rho/ROCK1 抑制检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f5/7053600/19dbab4ef291/aging-12-102719-g001.jpg

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