RETRACTED ARTICLE: The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

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.

POU2F1 Promotes Cell Viability and Tumor Growth in Gastric Cancer through Transcriptional Activation of lncRNA TTC3-AS1

“…Previous studies have demonstrated that POU2F1 plays a crucial role in promoting the progression of several tumors [ 10 , 18 , 29 , 30 ]. To determine the expression of POU2F1 and TTC3-AS1 in GC, 10 paired gastric tumor tissues and adjacent normal tissues were detected using qRT-PCR and western blot.…”

“…Analyses of public databases indicated that POU2F1 exhibited higher expression in renal, ovarian, and esophageal cancers while lower expression in the cerebral tumor, bladder cancer, and liposarcoma, compared with NCs. Recent studies have indicated that POU2F1 was highly expressed in GC patients [ 34 – 36 ]. In this study, we also identified that POU2F1 and its potential target TTC3-AS1 were significantly upregulated in GC tumor tissues, compared with normal tissues.…”

“…POU2F1 promotes growth and metastasis of hepatocellular carcinoma (HCC) through the FAT1 pathway [ 10 ]. With respect to GC, Xiao et al [ 34 ] have reported that POU2F1 directly bound to the promoter of tumor suppressor miR-4490 and inhibited its transcription to promote GC development and metastasis. Moreover, phosphorylation-activated AKT upregulates the expression of POU2F1, thus improving the expression of ECD (ecdysoneless homologue) in GC [ 35 ].…”

“…POU2F1 is also an independent prognostic factor in gastric cancer. Moreover, knockdown of POU2F1 leads to apparent inhibition of tumor proliferation and invasion in head and neck squamous cell carcinoma, gastric cancer, and so on [ 17 , 18 ]. Accumulated evidence has indicated that POU2F1 functions as an oncogene in tumor progression.…”

ssc-micorRNA-132 suppresses theClostridium perfringensbeta2 toxin induced inflammation and apoptosis of IPEC-J2 cells via targetingDACH1

“…MicroRNAs (miRNAs) are endogenous 19-23 nucleotide (nt) RNAs and pair with mRNAs of protein-coding genes to suppress translation and degrade mRNAs in post-transcriptional level (11). miRNAs are related to cellular proliferation, differentiation, apoptosis, migration, invasion and inflammation (12–16). Additionally, miRNAs play a crucial regulatory role in host immune response to pathogenic infection.…”