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miR-191-5p 通过抑制 SATB1 抑制 Wnt 通路抑制肺腺癌。

MiR-191-5p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway.

机构信息

Department of Cardiothoracic surgery, The People's Hospital of Bao'an Shenzhen, The Affiliated Bao'an Hospital of Southern Medical University, Shenzhen, China.

Department of Cardiothoracic surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Mol Genet Genomic Med. 2020 Jan;8(1):e1043. doi: 10.1002/mgg3.1043. Epub 2019 Nov 13.

Abstract

BACKGROUND

To investigate the function of miR-191-5p in lung adenocarcinoma and its possible mechanism.

METHODS

QRT-PCR was adopted for the detection of the expression levels of miR-191-5p and SATB1 (HGNC: 10541). The effects of miR-191-5p and SATB1 on cell proliferation and migration were examined through the CCK-8 and Transwell assays. Subsequently, the binding relationships between miR-191-5p and SATB1 were confirmed by dual-luciferase reporter gene assay. Finally, the potential mechanisms of action of miR-191-5p were explored through a serious of in vivo and in vitro experiments.

RESULTS

Lung adenocarcinoma patients had a notably lower expression level of miR-191-5p than controls, patients with metastasis had a lower level than those without metastasis, and the level in patients with lung adenocarcinoma in stage III-IV was lower than that in patients with lung adenocarcinoma in stage I-II. Overexpression of miR-191-5p repressed the migration and proliferation of lung cancer A549/H1650 cells. According to the reporter gene assay, miR-191-5p could bind to SATB1. Besides, SATB1 was significantly overexpressed in cancer tissues of patients with lung adenocarcinoma, and SATB1 overexpression accelerated the migration and proliferation of A549/H1650 cells and reversed inhibition on cell migration and proliferation by miR-191-5p.

CONCLUSION

Overexpression of miR-191-5p is capable of blocking the migration and proliferation of lung cancer cells, and its mechanism may be through targeting SATB1 thus downregulating Wnt signaling.

摘要

背景

研究 miR-191-5p 在肺腺癌中的作用及其可能的机制。

方法

采用 QRT-PCR 检测 miR-191-5p 和 SATB1(HGNC:10541)的表达水平。通过 CCK-8 和 Transwell 实验检测 miR-191-5p 和 SATB1 对细胞增殖和迁移的影响。随后,通过双荧光素酶报告基因实验证实 miR-191-5p 和 SATB1 之间的结合关系。最后,通过一系列体内和体外实验探讨 miR-191-5p 的潜在作用机制。

结果

肺腺癌患者 miR-191-5p 的表达水平明显低于对照组,有转移的患者低于无转移的患者,III-IV 期患者的表达水平低于 I-II 期患者。miR-191-5p 的过表达抑制了肺癌 A549/H1650 细胞的迁移和增殖。根据报告基因实验,miR-191-5p 可以与 SATB1 结合。此外,SATB1 在肺腺癌患者的癌组织中明显过表达,SATB1 的过表达加速了 A549/H1650 细胞的迁移和增殖,并逆转了 miR-191-5p 对细胞迁移和增殖的抑制作用。

结论

miR-191-5p 的过表达能够抑制肺癌细胞的迁移和增殖,其机制可能是通过靶向 SATB1 从而下调 Wnt 信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea7a/6978255/2101d709fc8a/MGG3-8-e1043-g001.jpg

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