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The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer.
- Source :
-
Cellular Oncology (2211-3428) . 2020, Vol. 43 Issue 6, p1017-1033. 17p. - Publication Year :
- 2020
-
Abstract
- Purpose: Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods: To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results: We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman's correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion: Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 22113428
- Volume :
- 43
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cellular Oncology (2211-3428)
- Publication Type :
- Academic Journal
- Accession number :
- 147387586
- Full Text :
- https://doi.org/10.1007/s13402-020-00553-1