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肝素酶通过miR-222/PPP2R2A/AKT轴促进前列腺癌上皮-间质转化和细胞侵袭。

Hepsin Promotes Epithelial-Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer.

作者信息

Li Ruiqian, Li Jun, Yang Hong, Bai Yu, Hu Chen, Wu Hongyi, Jiang Haiyang, Wang Qilin

机构信息

Department of Urology, Third Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 24;13:12141-12149. doi: 10.2147/OTT.S268025. eCollection 2020.

Abstract

PURPOSE

To determine the role and underlying mechanism of hepsin in epithelial-mesenchymal transition (EMT) and cell invasion in prostate cancer.

METHODS

The expression of hepsin in prostate cancer tissue samples and cell lines was measured by immunohistochemical staining and Western blotting. The EMT and cell invasion abilities of prostate cancer cells were detected by Western blot and transwell assays. RNA transfection was used to inhibit or overexpress related genes. The expression of miR-222 was detected by RT-qPCR. A dual‑luciferase reporter gene assay was performed to determine the target of miR-222.

RESULTS

Hepsin expression was upregulated in prostate cancer tissue samples and cell lines. Inhibition of hepsin attenuated EMT and cell invasion and downregulated the expression of miR-222. Decreased miR-222 expression enhanced the level of PPP2R2A, which in turn attenuated the AKT signaling. Activation of miR-222 or AKT could block the inhibitory effects on EMT and cell invasion induced by hepsin deficiency.

CONCLUSION

Hepsin promotes EMT and cell invasion through the miR-222/PPP2R2A/AKT axis in prostate cancer.

摘要

目的

确定肝素丝氨酸蛋白酶在前列腺癌上皮-间质转化(EMT)和细胞侵袭中的作用及潜在机制。

方法

采用免疫组织化学染色和蛋白质免疫印迹法检测前列腺癌组织样本和细胞系中肝素丝氨酸蛋白酶的表达。通过蛋白质免疫印迹法和Transwell实验检测前列腺癌细胞的EMT和细胞侵袭能力。利用RNA转染抑制或过表达相关基因。采用逆转录定量聚合酶链反应(RT-qPCR)检测miR-222的表达。进行双荧光素酶报告基因检测以确定miR-222的靶标。

结果

肝素丝氨酸蛋白酶在前列腺癌组织样本和细胞系中表达上调。抑制肝素丝氨酸蛋白酶可减弱EMT和细胞侵袭,并下调miR-222的表达。miR-222表达降低会增强蛋白磷酸酶2A调节亚基Bα(PPP2R2A)的水平,进而减弱AKT信号传导。激活miR-222或AKT可阻断肝素丝氨酸蛋白酶缺乏对EMT和细胞侵袭的抑制作用。

结论

在前列腺癌中,肝素丝氨酸蛋白酶通过miR-222/PPP2R2A/AKT轴促进EMT和细胞侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2a7/7701367/4c4183a10292/OTT-13-12141-g0001.jpg

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