MiR-195 Regulated by NEAT1 Attenuates the Docetaxel Resistance and Metastasis of Prostate Cancer Cells through Downregulating USP22

Yu Ren, Lihang Yu

Article ID: 6952
Vol 36, Issue 4, 2022
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20223604.106
Received: 8 September 2022; Accepted: 8 September 2022; Available online: 8 September 2022; Issue release: 8 September 2022

Abstract

Background: Currently, some patients with prostate cancer (PC) may develop resistance to docetaxel chemotherapy. Considering the reported regulatory effects of microRNA (miR)-195 and nuclear-enriched abundant transcript 1 (NEAT1) on the docetaxel resistance of PC cells, their interaction is discussed in this study. Methods: Docetaxel-resistant prostate cancer cells were established by long-term docetaxel stimulation. The upstream and downstream targets of miR-195 in PC cells were predicted and verified by bioinformatics analysis and dual-luciferase reporter assay. PC cells transfected with miR-195 inhibitor, shNEAT1, miR-195 mimic, or ubiquitin-specific protease 22 (USP22) overexpression plasmid, were treated with docetaxel. MTT assay, Transwell assay, and flow cytometry were used to determine the malignant behavior of PC cells and the half maximal inhibitory concentration (IC50) of docetaxel. Real-time quantitative PCR and western blot were used to quantify the expressions of NEAT1/miR-195/USP22 axis-related and metastasis-related factors. Results: MiR-195 was lowly expressed, while NEAT1 and USP22 were highly expressed in PC cells. Also, miR-195, while being sponged by NEAT1, could target USP22. MiR-195 mimic decreased the IC50 of docetaxel, migration, invasion, and the expressions of USP22, N-cadherin, and vimentin, while enhancing apoptosis and E-cadherin expression in docetaxel-resistant PC cells. USP22 overexpression increased the IC50 of docetaxel, migration and invasion, and reversed the regulatory effects of miR-195 mimic. Conclusions: MiR-195, modulated by NEAT1, attenuates docetaxel resistance and metastasis of PC cells by downregulating USP22.


Keywords

prostate cancer;microRNA (miR)-195;nuclear-enriched abundant transcript 1 (NEAT1);ubiquitin-specific protease 22 (USP22);docetaxel resistance;metastasis


References

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