RETRACTED ARTICLE: The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

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...

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Detalles Bibliográficos
Autores principales: Xiao, Yizhi, Liu, Side, Li, Jiaying, Dai, Weiyu, Tang, Weimei, Xiang, Li, Zhang, Wenjing, Lin, Jianjiao, Wang, Jing, Wu, Xiaosheng, Liu, Guangnan, Liu, Yuyang, Chen, Yaying, Zhu, Huiqiong, Wang, Yusi, Lin, Zhizhao, Yang, Qiong, Chen, Tianming, Sun, Yong, Li, Aimin, Xiong, Jing, Wang, Jide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2020
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716863/
https://www.ncbi.nlm.nih.gov/pubmed/32857323
http://dx.doi.org/10.1007/s13402-020-00553-1
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13402-020-00553-1) contains supplementary material, which is available to authorized users.

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