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The present results indicate that miR122 serves a tumorpromoting role by direct targeting FOXO3 in clear cell renal cell carcinoma.
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Longevity-associated FOXO3 variants may be associated with lower blood pressure and essential hypertension in Japanese women.
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Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. [review]
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In liver cancer cell lines, inhibition the activity of PI3K/Akt signaling pathway significantly decreased the levels of phosphorylated FOXO3a and increased the total levels of FOXO3a, which was accompanied by the accumulation of nuclear FOXO3a. Moreover, cell proliferation of liver cancer cells was significantly suppressed by inhibition the PI3K/Akt/FOXO3a signaling pathway.
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Mechanistically, authors found miR-10b-3p regulated FOXO3 expression by directly binding to the 3'-untranslated region.
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The significant association between forkhead box protein O3 (FOXO3) single nucleotide polymorphisms (SNPs) and longevity has been independently replicated in multiple populations including a genome-wide association study [Review].
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Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription.
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expression significantly deceased in degenerated discs
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Loss of FOXO3 expression due to O-GlcNAcylation is associated with tumorigenesis.
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This study revealed a novel mechanism for prostate cancer metastasis that involves SIRT3/ Wnt/beta-catenin/ FOXO3A signaling to modulate EMT and cell migration.
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Study findings present a novel mechanism that controls FOXO3 activation and revealed that SIRT6 is a pivotal regulatory factor in determining liver cancer chemosensitivity. SIRT6 interacts with FOXO3 and this interaction increases FOXO3 ubiquitination and decreases its stability.
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FOXO3a activation induces vascular smooth muscle cell apoptosis and extracellular matrix breakdown, in part, because of transcriptional activation of MMP13. FOXO3a activation promotes atherosclerosis and medial degeneration and increases neointima after injury that is partly dependent on MMP13.
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The finding suggested that miR-30c-5p might play essential role in NLRP3 inflammasome-modulated cell pyroptosis by targeting FOXO3 in human aortic endothelial cells.
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The cardiac regeneration may be promoted by proper control of FOXO1/3 activity. FOXO1 mainly plays a detrimental role in heart while FOXO3's actions are influenced by cell type. [review]
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role in autophagy activation and the maintenance of intracellular homeostasis in inflamed odontoblasts
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Low FOXO3A expression is associated with colorectal cancer.
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FoxO3a was overexpressed in 64.71% cases of hepatocellular carcinoma (HCC). FoxO3a overexpression was associated with aggressive phenotypes of HCC, such as histologic grade, stage, and small vessel invasion. FoxO3a overexpression was also correlated with poor disease-free survival. Downregulation of FoxO3a in a HepG2 cell line inhibited cell proliferation and migration.
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stable knockdown of FOXO3, NCOA3, and TCF7L2 restored growth in low glucose but reduced MEK/MAPK phosphorylation, reduced anchorage-independent growth, and modulated expressions of GLUT1 and Ras pathway related proteins.
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A better understanding of the mechanisms regulating the FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and functions, may render these proteins reliable and early diagnostic/prognostic factors as well as crucial therapeutic targets for cancer treatment and importantly, for overcoming chemotherapeutic drug resistance.
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the inhibition of miR-9 could induce apoptosis in cervical cancer by targeting FOXO3.
