The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer
- PDF / 24,727,554 Bytes
- 17 Pages / 595.276 x 790.866 pts Page_size
- 74 Downloads / 156 Views
ORIGINAL ARTICLE
The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer Yizhi Xiao 1 & Side Liu 1,2 & Jiaying Li 1 & Weiyu Dai 1 & Weimei Tang 1 & Li Xiang 2 & Wenjing Zhang 3 & Jianjiao Lin 1,2 & Jing Wang 1 & Xiaosheng Wu 1 & Guangnan Liu 1 & Yuyang Liu 4 & Yaying Chen 5 & Huiqiong Zhu 1 & Yusi Wang 1 & Zhizhao Lin 1 & Qiong Yang 1,6 & Tianming Chen 1 & Yong Sun 1 & Aimin Li 1 & Jing Xiong 1 & Jide Wang 1,2 Accepted: 18 August 2020 # The Author(s) 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. Keywords Gastric cancer . Metastasis . MiR-4490 . POU2F1 . Epithelial-mesenchymal transition
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00553-1) contains supplementary material, which is available to authorized users. * Aimin Li [email protected]
3
Department of Medical Oncology, the First people’s Hospital of Yunnan Province, Medical School of Kunming University of Science and Technology, Kunming 650032, China
4
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, People’s Republic of China
5
Department of Gastroenterology, The third affiliated hospital of Guangzhou medical university, Guangzhou 510150, China
6
The Second Affiliated Hospital of University of Sout
