FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating the APC2/β-Catenin Axis

Sun, Yan; Wang, Lin; Xu, Xuehu; Han, Puqing; Chen, Zuanguang; Tian, Xuan; Li, Mingsong

doi:10.3389/fcell.2021.659731

Cited by 15 publications

(11 citation statements)

References 29 publications

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“…[9,27] Additionally, FoxO4 was reported to involve in healing of gastric ulcers induced by WRS through regulation of apoptosis and a decreased of APC2 and p(S37)-β-catenin positively correlated with FoxO4 also be reported, which suggests potential function of FoxO4 as tumor suppressor through upregulation of APC and Wnt/β-catenin pathway. [38,39] In our study, we similarly found that the expression of Keap-1 and FoxO4 was related with tumor differentiation. All these suggest potential relationship between aforementioned proteins with the severity and prognosis of CRC patients.…”

Section: Discussionsupporting

confidence: 69%

“…[4] Furthermore, FoxO4 can inhibit expression of glucose transporter-1, erythropoietin, and vascular endothelial growth factor, which is crucial in tumor expansion and tumor progression. [37] Sun et al [38] also showed that FoxO4 overexpression substantially decreased CRC cells migration and in vivo metastasis. Consistent with these results, we also found that the expression of ALD, Keap-1, and FoxO4 were significantly associated with tumor location.…”

Section: Discussionmentioning

confidence: 99%

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Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma

Huang

Wang

et al. 2022

Medicine

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Aldolase A (A-2) (ALD), Kelch-like-ECH associated protein-1 (Keap-1), and Forkhead box O4 (FoxO4) are key regulatory proteins, which have been proven to be involved in tumor development. However, the clinicopathological significance of ALD, Keap-1, and FoxO4 expressions in colorectal (colon) carcinoma (CRC) is not clearly known. We sought to explore the clinicopathological significance of ALD, Keap-1, and FoxO4 in CRC to provide evidences for potential monitoring index of CRC. Cases of 199 CRC patients were analyzed retrospectively. Evaluation of ALD, cAMP response element-binding protein-2, cyclo-oxygenase 2, FoxO4, Keap-1, and p53 expressions in CRC patients was accomplished with immunohistochemical technique. The patients were divided into negative and positive groups in accordance with immunohistochemical result. We compared the clinicopathological characteristics of the patients in the 2 groups, coupled with analysis of the relationship between 6 aforesaid proteins and clinicopathological characteristics. Herein, we confirmed the association of tumor location with the expression of ALD, Keap-1, and FoxO4. Also, tumor differentiation was observed to associate significantly with the expression of Keap-1, FoxO4, and Cox-2. The data also revealed that there was a correlation between smoking and expression of ALD, Keap-1, FoxO4, p53, and Cox-2. Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma

Huang

Wang

et al. 2022

Medicine

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“…This reversal of expression might be an outcome of concomitant diabetes in ECD patients. Adenomatous polyposis coli protein 2 (APC) is a tumor suppressor protein that plays a role in cell migration, cell adhesion, proliferation, and differentiation It suppresses the Wnt/β-catenin pathway which is essential for epithelial–mesenchymal transition in many tumor cells . In human ovarian cells, downregulation of APC2 by miR-939 is required for cell proliferation .…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes

Mujammami,

Rafiullah,

Akkour

et al. 2024

ACS Omega

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The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients.

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“…However, whether miR‐3194‐5p promotes CRC progression by targeting galectin‐7 is worth further study. Among the various miR‐3194‐5p target genes predicted by the database, adenomatous polyposis coli 2, 36 KLF13, 37 and LDLRAD4 38 play anticancer roles in CRC. However, further study is required to determine whether miR‐3194‐5p promotes the occurrence and development of CRC through targeted inhibition of these genes.…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin inhibits colorectal cancer cell stemness through the miR‐3194‐5p/catenin beta‐interacting protein 1 axis

Su,

Hu,

et al. 2023

The Kaohsiung J of Med Scie

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Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real‐time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit‐8, clone‐formation, and transwell migration and invasion assays, respectively. The sphere‐formation capacity was determined using the sphere‐formation assay. A dual‐luciferase reporter gene assay was employed to analyze the interaction between miR‐3194‐5p and catenin beta‐interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial–mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR‐3194‐5p was upregulated in CRC tissues and cells. MiR‐3194‐5p knockdown suppressed CRC cell stemness, while miR‐3194‐5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR‐3194‐5p overexpression. CTNNBIP1 functioned as the target of miR‐3194‐5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β‐catenin signaling activation by PF.PF regulated the miR‐3194‐5p/CTNNBIP1/Wnt/β‐catenin axis to repress CRC cell stemness.

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FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating the APC2/β-Catenin Axis

Cited by 15 publications

References 29 publications

Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma

Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma

Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes

Paeoniflorin inhibits colorectal cancer cell stemness through the miR‐3194‐5p/catenin beta‐interacting protein 1 axis

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