FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients

Khan, Mateen A.; Massey, Sheersh; Ahmad, Irfan; Sadaf, -; Akhter, Naseem; Habib, M.; Mustafa, Saad; Deo, Svs; Husain, Syed Akhtar

doi:10.3389/fgene.2022.842943

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…It was found that changes in FOXO1 gene expression depended on patient age, with higher expressions observed in the tumor tissue of patients above the median age of the studied group (68 years) compared to the younger group. Comparable results were obtained by Khan et al, who demonstrated higher FOXO1 expression in breast cancer tissue of patients aged above 50 years compared to those under 50 years [ 19 ].…”

Section: Discussionmentioning

confidence: 65%

Genetic Insights into Colorectal Cancer: Evaluating PI3K/AKT Signaling Pathway Genes Expression

Świechowski,

Pietrzak,

Wosiak

et al. 2024

IJMS

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The PI3K/AKT pathway plays a pivotal role in cellular processes, and its dysregulation is implicated in various cancers, including colorectal cancer. The present study correlates the expression levels of critical genes (PIK3CA, PTEN, AKT1, FOXO1, and FRAP) in 60 tumor tissues with clinicopathological and demographic characteristics. The results indicate age-related variation in FOXO1 gene expression, with higher levels observed in patients aged 68 and above. In addition, tumors originating from the rectum exhibit higher FOXO1 expression compared to colon tumors, suggesting region-specific differences in expression. The results also identify the potential correlation between PTEN, PIK3CA gene expression, and parameters such as tumor grade and neuroinvasion. The bioinformatic comparative analysis found that PTEN and FOXO1 expressions were downregulated in colorectal cancer tissue compared to normal colon tissue. Relapse-free survival analysis based on gene expression identified significant correlations, highlighting PTEN and FRAP as potential indicators of favorable outcomes. Our findings provide a deeper understanding of the role of the PI3K/AKT pathway in colorectal cancer and the importance of understanding the molecular basis of colorectal cancer development and progression.

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Section: Discussionmentioning

confidence: 65%

Genetic Insights into Colorectal Cancer: Evaluating PI3K/AKT Signaling Pathway Genes Expression

Świechowski,

Pietrzak,

Wosiak

et al. 2024

IJMS

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“…These two genes are known as tumor suppressors and have been described in several types of cancer, such as prostate [36][37][38][39], colorectal [40][41][42] and breast cancer [43][44][45], as well as in HCC [46][47][48][49]. Foxo1 is a member of the widely expressed Foxo transcription factor family, which also includes Foxo3/4/6.…”

Section: Discussionmentioning

confidence: 99%

MiR-182-5p Is Upregulated in Hepatic Tissues from a Diet-Induced NAFLD/NASH/HCC C57BL/6J Mouse Model and Modulates Cyld and Foxo1 Expression

Compagnoni

Capelli

Zelli

et al. 2023

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is considered a relevant liver chronic disease. Variable percentages of NAFLD cases progress from steatosis to steatohepatitis (NASH), cirrhosis and, eventually, hepatocellular carcinoma (HCC). In this study, we aimed to deepen our understanding of expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from C57BL/6J mouse models of diet-induced NAFL/NASH/HCC progression. A miR-182-5p increase was detected early in livers as NAFLD damage progressed, and in tumors compared to peritumor normal tissues. An in vitro assay on HepG2 cells confirmed Cyld and Foxo1, both tumor-suppressor, as miR-182-5p target genes. According to miR-182-5p expression, decreased protein levels were observed in tumors compared to peritumor tissues. Analysis of miR-182-5p, Cyld and Foxo1 expression levels, based on datasets from human HCC samples, showed results consistent with those from our mouse models, and also highlighted the ability of miR-182-5p to distinguish between normal and tumor tissues (AUC 0.83). Overall, this study shows, for the first time, miR-182-5p overexpression and Cyld-Foxo1 downregulation in hepatic tissues and tumors from a diet-induced NAFLD/HCC mouse model. These data were confirmed by the analysis of datasets from human HCC samples, highlighting miR-182-5p diagnostic accuracy and demonstrating the need for further studies to assess its potential role as a biomarker or therapeutic target.

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“… 41 , 42 In addition, down-regulation of FOXO1 expression and promoter hypermethylation has been identified in breast cancer tissues, and correlated with tumor size and lymph node metastasis. 43 Patients with breast cancer with high FOXO1 expression have better prognosis. 44 A study of Zeng et al reported that FOXO1 was associated with immune cell infiltration, immune checkpoint expression, and response to immunotherapy in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis

Yu,

Wang,

Shen

et al. 2023

BCTT

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Background This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC. Materials and Methods Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients’ clinicopathological characteristics and prognostic prediction. A dual-luciferase reporter assay was used to determine the relationship between hsa_circ_0007823, miR-182-5p, and FOXO1. The effect of circ_0007823 overexpression on the growth of TNBC cells was investigated in vitro and in vivo. Results Lower levels of hsa_circ_0007823 were found in TNBC tissues and cell lines and were closely associated with lymph node metastasis, poorer overall and disease-free survival rates. MiR-182-5p was significantly up-regulated, whereas FOXO1 was down-regulated in TNBC cell lines. The miR-182-5p inhibition up-regulated FOXO1 in TNBC cells. Dual-luciferase reporter assays showed that hsa_circ_0007823, miR-182-5p, and FOXO1 interacted with each other. Overexpression of circ_0007823 significantly inhibited the viability, migration, and invasion of TNBC cell lines, but promoted apoptosis. In vivo experiments showed that circ_0007823 overexpression inhibited tumor growth and down-regulated miR-182-5p and up-regulated FOXO1. Conclusion Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.

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FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients

Cited by 9 publications

References 23 publications

Genetic Insights into Colorectal Cancer: Evaluating PI3K/AKT Signaling Pathway Genes Expression

Genetic Insights into Colorectal Cancer: Evaluating PI3K/AKT Signaling Pathway Genes Expression

MiR-182-5p Is Upregulated in Hepatic Tissues from a Diet-Induced NAFLD/NASH/HCC C57BL/6J Mouse Model and Modulates Cyld and Foxo1 Expression

Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis

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