The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review

Khan, M. Rehan; Sarkar, Devanand

doi:10.3390/genes12020308

Cited by 17 publications

(11 citation statements)

References 132 publications

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“…Similarly, AEG-1 protein expression was analyzed in this study by IHC which showed overexpression of AEG-1 protein in primary CRC tissues compared to normal tissues [2]. AEG-1 might serve as a prognostic marker in CRC as all studies exhibited that level of AEG-1 increases with CRC progression and negatively correlate with overall survival [108]. In HCC, IHC analysis of 323 patients exhibited significant AEG-1 overexpression in 54.2% of the patients.…”

Section: Overview On Clinicopathological Significance Of Aeg-1 In Different Cancer Typesmentioning

confidence: 69%

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

Sriramulu

Sun

Malayaperumal

et al. 2021

Cells

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Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-κB; (iii) the ERK or mitogen-activated protein kinase and Wnt or β-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.

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Section: Overview On Clinicopathological Significance Of Aeg-1 In Different Cancer Typesmentioning

confidence: 69%

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

Sriramulu

Sun

Malayaperumal

et al. 2021

Cells

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“…Furthermore, our findings showed that MTDH, which is a type of scaffold protein, was regulated by miR-21-3p. MTDH is reported to participate in many key oncogenic pathways, including the Wnt signaling pathway by interacting with related proteins (Khan and Sarkar, 2021). The relationship between Wnt signaling and intestinal barrier dysfunction is complex and has never been truly determined.…”

Section: Discussionmentioning

confidence: 99%

TNF-α–Induced miR-21-3p Promotes Intestinal Barrier Dysfunction by Inhibiting MTDH Expression

et al. 2021

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Intestinal barrier dysfunction is characterized by increased intestinal permeability to lumen endotoxin, showing remarkable predisposition to immune enteropathy, and colorectal cancer tumor necrosis factor (TNF)-α is associated with this pathological process, while the mechanism remains unknown. In this study, different doses of TNF-α were used for Caco-2 cell treatment. We discovered that miR-21-3p expression was obviously increased by TNF-α in a dose-dependent manner. Further study demonstrated that TNF-α could upregulate miR-21-3p expression through the NF-κB signaling pathway. Then, TargetScan and miRWalk miRNA–mRNA interaction prediction online tools were introduced, and metadherin (MTDH) was screened out as a potential target of miR-21-3p. We subsequently found that miR-21-3p could directly target the 3′-untranslated region (UTR) of MTDH mRNA and inhibit its expression. Furthermore, it was demonstrated that miR-21-3p could regulate the Wnt signaling pathway by targeting MTDH mRNA, suggesting the effect of miR-21-3p/MTDH/Wnt axis on intestinal barrier dysfunction. Our findings provide a novel potential biomarker and therapeutic target for intestinal barrier dysfunction and related diseases.

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“…Wnt signaling further promotes the EMT process, whilst suppressing autophagy. The TGF-β2/RSmads signaling pathway induced autophagy in gliomas, and has been reported to take place through AEG-1/MTDH activation [ 41 ], identified as a prominent oncogene [ 42 ]. Autophagy is essential in TGF-β-induced glioblastoma, whilst TGF-β is one of the most noticeable drivers of EMT, emphasizing the importance of the autophagy/TGF-β/EMT pathway as a therapeutic target for glioblastoma.…”

Section: Drivers Of Emt In Glioblastomamentioning

confidence: 99%

MicroRNA Interrelated Epithelial Mesenchymal Transition (EMT) in Glioblastoma

Damane

Hull

Reis

et al. 2022

Genes

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MicroRNAs (miRNA) are small non-coding RNAs that are 20–23 nucleotides in length, functioning as regulators of oncogenes or tumor suppressor genes. They are molecular modulators that regulate gene expression by suppressing gene translation through gene silencing/degradation, or by promoting translation of messenger RNA (mRNA) into proteins. Circulating miRNAs have attracted attention as possible prognostic markers of cancer, which could aid in the early detection of the disease. Epithelial to mesenchymal transition (EMT) has been implicated in tumorigenic processes, primarily by promoting tumor invasiveness and metastatic activity; this is a process that could be manipulated to halt or prevent brain metastasis. Studies show that miRNAs influence the function of EMT in glioblastomas. Thus, miRNA-related EMT can be exploited as a potential therapeutic target in glioblastomas. This review points out the interrelation between miRNA and EMT signatures, and how they can be used as reliable molecular signatures for diagnostic purposes or targeted therapy in glioblastomas.

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The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review

Cited by 17 publications

References 132 publications

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

TNF-α–Induced miR-21-3p Promotes Intestinal Barrier Dysfunction by Inhibiting MTDH Expression

MicroRNA Interrelated Epithelial Mesenchymal Transition (EMT) in Glioblastoma

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