5-Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT-Dependent and Independent Manners.

摘要: Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member serotonergic system, hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that 5-HT1D expression level was significantly up-regulated HCC tissues cell lines. closely correlated with unfavorable clinicopathological characteristics. Survival analyses show elevated predicts poor overall survival high recurrence probability patients. Functional studies revealed promoted proliferation, epithelial-mesenchymal transition, metastasis vitro vivo. Mechanistically, could stabilize PIK3R1 by inhibiting ubiquitin-mediated degradation. interaction between phosphoinositide-3-kinase subunit 1 (PIK3R1) enhanced FoxO6 through PI3K/Akt signaling pathway; also be directly transcriptionally activated Akt-independent manner. MicroRNA-599 found upstream suppressive modulator 5-HT1D. Additionally, attenuate tryptophan hydroxylase PI3K/Akt/cut-like homeobox axis HCC. Conclusion: Herein, we uncovered potent oncogenic effect on interacting activate PI3K/Akt/FoxO6 pathway, provided a potential therapeutic target for