EZH2‐mediated downregulation of miR‐155‐5p contributes to prostate cancer cell malignancy through SMAD2 and TAB2
Abstract miR‐155 exhibits variable expression in different tumors and fulfills diverse biological roles. However, specific molecular mechanisms by which miR‐155‐5p, which is under‐expressed in prostate cancer (PCa), operates are yet to be elucidated. The role of the enhancer of zeste 2 (EZH2)/miR‐15...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-03-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12936 |
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| Summary: | Abstract miR‐155 exhibits variable expression in different tumors and fulfills diverse biological roles. However, specific molecular mechanisms by which miR‐155‐5p, which is under‐expressed in prostate cancer (PCa), operates are yet to be elucidated. The role of the enhancer of zeste 2 (EZH2)/miR‐155‐5p axis in PCa was determined by using bioinformatics tools and performing luciferase reporter assay, chromatin immunoprecipitation PCR, CCK‐8 assays, cell migration and invasion assays, RNA isolation, reverse transcription quantity (RT‐qPCR) and Western blot. miR‐155‐5p expression would be reduced and promoter methylation would increase in PCa. After 5‐Aza‐CdR treatment and the integration of the upstream promoter of miR‐155‐5p into a pGL3‐basic/luciferase construct, fluorescence reporter analysis showed that promoter hypermethylation mediated the suppression of miR‐155‐5p in PCa. Furthermore, EZH2 attached to the miR‐155‐5p promoter and modulated its expression. EZH2 facilitated the suppression of miR‐155‐5p through enhanced H3K27me3 methylation, considerably affecting its expression. Through dual‐luciferase assays, SMAD2 and TAB2 were confirmed as downstream targets of miR‐155‐5p, regulating the PCa cellular phenotype governed by miR‐155‐5p. Lastly, 5‐Aza‐CdR regulated miR‐155‐5p expression by modulating its promoter methylation and influenced the malignant behavior of PCa cells. EZH2 promotes H3K27me3 methylation, repressing miR‐155‐5p expression, which subsequently upregulates the downstream targets SMAD2 and TAB2 and promotes PCa cell proliferation, epithelial–mesenchymal transition (EMT), migration and invasion. |
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| ISSN: | 1607-551X 2410-8650 |