Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review)

Li, Xiudan; Wan, Tingting; Li, Yanbo

doi:10.3892/etm.2021.10139

Cited by 14 publications

(8 citation statements)

References 83 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We then measured miR-449a promoter activity by cloning three promoter regions, 500 base-pair (bp), 1000 bp, and 2000 bp, upstream of the miR-449a transcription starting site in the luciferase reporter plasmid (pGL3-Basic), and found that the luciferase activity of 2000 bp miR-449a luciferase reporter plasmid increased about 10-fold after autophagy induction ( Figure 2D ), suggesting that autophagy increases miR-449a activity within the promoter region of 1000 to 2000 bp. Transcription factor FoxO1 has been demonstrated to be involved in cellular mechanisms including cell proliferation, differentiation, apoptosis, and autophagy ( 25 ). We predicted two FoxO1 binding sites within the region of 1000 to 2000 bp upstream of the miR-449a transcriptional starting site using the TFSEARCH software program.…”

Section: Resultsmentioning

confidence: 99%

Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer

et al. 2021

View full text Add to dashboard Cite

Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.

show abstract

Section: Resultsmentioning

confidence: 99%

Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…As the most widely studied subtype of the FoxO family, FoxO1 is commonly involved in the regulation of cell metabolism, apoptosis, and differentiation, especially in pancreatic β-cell (86)(87)(88). FoxO1 is a critical transcription factor in insulin cascade affected by different upstream signaling molecules [e.g., phosphatidylinositol 3-kinase (PI3K)/Akt, AMP-activated protein kinase (AMPK), and Sirtuin 1 (SIRT 1)], and it can regulate several downstream proteins, including myocardial pyruvate dehydrogenase (PDH) and peroxisome proliferator-activated receptor α (PPARγ) coactivator-1α (PGC-1α) (89)(90)(91)(92).…”

Section: Discussionmentioning

confidence: 99%

Research status and trends of the diabetic cardiomyopathy in the past 10 years (2012–2021): A bibliometric analysis

Wang

Tian²,

Gao³

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundDiabetic cardiomyopathy is one of the most life-threatening diabetic complications. However, the previous studies only discuss a particular aspect or characteristic of DCM, the current state and trends were explored by limited research. We aimed to perform a systemically bibliometric study of DCM research progress status in the past decade, visualize the internal conceptual structure and potential associations, and further explore the prospective study trends.MethodsArticles related to DCM published from January 2012 to December 2021 were collected in the Web of Science core collection (WoSCC) database on June 24, 2022. We exported all bibliographic records, including titles, abstracts, keywords, authorship, institutions, addresses, publishing sources, references, citation times, and year of publication. In addition, the journal Impact Factor and Hirsch index were obtained from the Journal Citation Report. We conducted the data screening, statistical analysis, and visualization via the Bibliometrix R package. VOS viewer software was employed to generate the collaboration network map among countries and institutions for better performance in visualization.ResultsIn total, 1,887 original research articles from 2012 to 2021 were identified. The number of annual publications rapidly increased from 107 to 278, and a drastic increase in citation times was observed in 2017–2019. As for global contributions, the United States was the most influential country with the highest international collaboration, while China was the most productive country. Professor Cai Lu was the most prolific author. Shandong University published the most articles. Cardiovascular Diabetology journal released the most DCM-related articles. “Metabolic Stress-induced Activation of FoxO1 Triggers Diabetic Cardiomyopathy in Mice” Battiprolu PK et al., J Clin Invest, 2012. was the most top-cited article regarding local citations. The top three keywords in terms of frequency were apoptosis, oxidative stress, and fibrosis. The analysis of future topic trends indicated that “Forkhead box protein O1,” “Heart failure with preserved ejection fraction,” “Dapagliflozin,” “Thioredoxin,” “Mitochondria dysfunction,” “Glucose,” “Pyroptosis,” “Cardiac fibroblast” and “Long non-coding RNA” could be promising hotspots.ConclusionThis study provides meaningful insights into DCM, which is expected to assist cardiologists and endocrinologists in exploring frontiers and future research directions in the domain through a refined and concise summary.

show abstract

“…The transformation of glucose into glycogen is controlled by various enzymes, but insulin is the one that initiates it. The insulin receptor downregulates the activity of the protein phosphatase 2A via the Pi3k-Akt-mTOR and mitogen-activated protein kinases signaling pathways [23]. The transformation of glycogen in glucose is regulated by glucagon.…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, the analysis of the presented dataset revealed an increased expression of FOXO1 (Forkhead Box O1) gene in fibroblasts. The ability of the FOXO1 gene to aggravate glucophagy in diabetic cardiomyopathy, and the role of FOXO1 in dilated cardiomyopathy in type 2 diabetes mellitus have been reported [23]. FOXO1 activation is dependent on the AKT signaling pathway, which is downregulated in RBCK1 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Additional Pathogenic Pathways in RBCK1 Deficiency

Demicheva¹,

Shinwari²,

Ushenin³

et al. 2022

Math.Biol.Bioinf.

View full text Add to dashboard Cite

RBCK1 deficiency is a rare congenital autoinflammatory disease that causes inflammatory disruption on the molecular level. This deficiency has three major clinical manifestations: increased sensitivity to bacterial infections, autoinflammation syndrome, and the accumulation of amylopectin in skeletal muscle. The amylopectinosis causes myopathy and cardiomyopathy. The pathogenesis of the disease is poorly investigated and may include unnoticed relationships. We performed gene expression analysis on patients with RBCK1 deficiency and three other autoinflammatory diseases. The identification of differentially expressed genes revealed a large number of downregulated genes that are involved in the activation of essential metabolic and immune pathways, including NF-kB and Pi3k-Akt-mTOR. Signaling pathways were analysed using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and Gene Ontology resource. Predicted protein-protein interactions were retrieved from the STRING (Search Tool for the Retrieval of Interacting proteins database). Besides the primary involvement of RBCK1 in disease pathology, several downregulated pathways aggravate symptoms of myopathy, cardiomyopathy, and bacterial disease. The studied pathways may serve as new targets for the development of compensatory therapies for patients with RBCK1 deficiency.

show abstract

Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review)

Cited by 14 publications

References 83 publications

Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer

Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer

Research status and trends of the diabetic cardiomyopathy in the past 10 years (2012–2021): A bibliometric analysis

Additional Pathogenic Pathways in RBCK1 Deficiency

Contact Info

Product

Resources

About