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Effects of LncRNA FOXP4⁃AS1 regulating EZH2/LATS2 axis on proliferation and migration of bladder urothelial cancer cells
Objective To investigate the impact of LncRNA FOXP4-AS1 regulating the EZH2/LATS2 axis on the proliferation and migration of bladder urothelial carcinoma （BUC） cells. Methods The Cancer Genome Atlas （TCGA） database and real-time quantitative PCR were utilized to analyze the expression of FOXP4-AS1 and LATS2 mRNA in BUC tissues. Cell proliferation was observed using MTT experiments， and migration was checked using Transwell assays. Western blot assays were performed to determine the expression of LATS2 and H3K27me3 proteins. RNA immunoprecipitation （RIP） and chromatin immunoprecipitation （ChIP） assays were employed to verify the relationship between FOXP4-AS1， EZH2 and LATS2. Results Compared with normal bladder tissues， FOXP4-AS1 expression was increased in tumor tissues， while LATS2 mRNA expression was decreased （P < 0.01）. Moreover， FOXP4-AS1 expression was elevated in EJ， T24， BIU-87， and 5637 cell lines compared to SV-HUC-1 （P < 0.01）. The inhibition of FOXP4-AS1 resulted in a significant decrease in the proliferation， migration， and expression of H3K27me3 protein in BUC cells， while concurrently upregulating the expression of LATS2 mRNA and protein. Conversely， the overexpression of FOXP4-AS1 yielded contrasting effects （P < 0.05）. RIP and ChIP assays revealed that FOXP4-AS1 could recruit EZH2 to the promoter region of LATS2， leading to an enrichment of H3K27me3 in this region. Interference with LATS2 or EZH2 expression partially reversed the effects of FOXP4-AS1 silencing or overexpression on the proliferation and migration of BUC cells， with concomitant effects on LATS2 expression. Conclusion FOXP4-AS1 demonstrates a notable increase in expression in BUC， leading to a suppression of LATS2 expression through the recruitment of EZH2 to the promoter region of LATS2. This regulatory process ultimately influences the proliferation and migration of BUC cells.
Key words： bladder urothelial carcinoma; FOXP4-AS1; EZH2; LATS2
Wei XIANG , Lei LYU , Fuxin ZHENG , Jingdong YUAN , Gaofeng ZHOU . Effects of LncRNA FOXP4⁃AS1 regulating EZH2/LATS2 axis on proliferation and migration of bladder urothelial cancer cells[J]. The Journal of Practical Medicine, 2024 , 40(20) : 2819 -2827 . DOI: 10.3969/j.issn.1006-5725.2024.20.002
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