HnRNP-F promotes the proliferation of bladder cancer cells mediated by PI3K/AKT/FOXO1

被引:19
作者
Li, Fei [1 ]
Xie, Weiwei [1 ]
Fang, Yunze [1 ]
Xie, Kunfeng [1 ]
Liu, Wendong [1 ]
Hou, Lina [2 ]
Tan, Wanlong [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Nanfang Hosp, Dept Hlth Management, Guangzhou 510515, Guangdong, Peoples R China
来源
JOURNAL OF CANCER | 2021年 / 12卷 / 01期
关键词
Heterogeneous nuclear ribonucleoprotein F; Phosphoinositide 3-kinase/protein kinase B signalling pathway; Bladder cancer; Forkhead box O1; Proliferation; SIGNALING PATHWAY; ACTIVATION;
D O I
10.7150/jca.50490
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Our previous study showed that heterogeneous nuclear ribonucleoprotein F (hnRNP-F) could induce epithelial-mesenchymal transition and metastasis in bladder cancer (BC), however, the role and mechanism of hnRNP-F in mediating the proliferative ability of BC cells remain unclear. HnRNP-F promoted the proliferation of BC cells by using BC cell lines and cell counting kit-8 (CCK8), colony formation and flow cytometry assays in vitro. Furthermore, the association of hnRNP-F with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway was confirmed by western blotting after bioinformatic analysis. HnRNP-F expression was significantly decreased by treatment with the PI3K/AKT signalling pathway inhibitor LY294002, whereas hnRNP-F knockdown did not significantly affect PI3K or AKT expression, suggesting that hnRNP-F is likely a downstream target of the PI3K/AKT pathway. Forkhead box O1 (FOXO1) is a molecule downstream of PI3K/AKT and can be inhibited by phosphorylation. In addition, chromatin immunoprecipitation (ChIP) and luciferase reporter assays indicated that FOXO1 expression was negatively correlated with hnRNP-F expression as FOXO1 was found to bind to the promoter region of hnRNP-F mRNA and inhibit its transcription. To sum up, our findings suggest that hnRNP-F expression is regulated by the PI3K/AKT-mediated phosphorylation of FOXO1, with phosphorylation inhibiting FOXO1, which subsequently allows hnRNP-F to promote proliferation. This finding is a novel discovery in BC and could help reveal the mechanism of BC progression.
引用
收藏
页码:281 / 291
页数:11
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