The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Muthu, Manikandan; Chun, Se Chul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae‐Hyoung; Oh, Jae-Wook

doi:10.3390/ijms21155583

Cited by 9 publications

(7 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AP5M1 (a.k.a. MUDENG ), the GMR of nodule “B”, is already considered a target for anti-cancer therapy owing to its pro-apoptotic function [ 73 ]. Owing to its very low expression variability, the 20% increase of AP5M1 expression level in the nodule “B” was statistically significant.…”

Section: Resultsmentioning

confidence: 99%

A Personalized Genomics Approach of the Prostate Cancer

Iacobaş

2021

Cells

View full text Add to dashboard Cite

Decades of research identified genomic similarities among prostate cancer patients and proposed general solutions for diagnostic and treatments. However, each human is a dynamic unique with never repeatable transcriptomic topology and no gene therapy is good for everybody. Therefore, we propose the Genomic Fabric Paradigm (GFP) as a personalized alternative to the biomarkers approach. Here, GFP is applied to three (one primary—“A”, and two secondary—“B” & “C”) cancer nodules and the surrounding normal tissue (“N”) from a surgically removed prostate tumor. GFP proved for the first time that, in addition to the expression levels, cancer alters also the cellular control of the gene expression fluctuations and remodels their networking. Substantial differences among the profiled regions were found in the pathways of P53-signaling, apoptosis, prostate cancer, block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy, and sustained angiogenesis. ENTPD2, AP5M1 BAIAP2L1, and TOR1A were identified as the master regulators of the “A”, “B”, “C”, and “N” regions, and potential consequences of ENTPD2 manipulation were analyzed. The study shows that GFP can fully characterize the transcriptomic complexity of a heterogeneous prostate tumor and identify the most influential genes in each cancer nodule.

show abstract

Section: Resultsmentioning

confidence: 99%

A Personalized Genomics Approach of the Prostate Cancer

Iacobaş

2021

Cells

View full text Add to dashboard Cite

show abstract

“…MuD was initially known to be involved in cell death in cytotoxic T cells [ 47 ]. A previous study suggested that Bid activation may occur prior to MuD degradation induced by death stimuli, while Bid cleavage can occur prior to MuD activation and plays an important role in MuD′s functional properties in TRAIL-mediated apoptotic signaling [ 48 ]. Strikingly, a similar pattern was observed in our results—Bid cleavage occurred prior to MuD activation, while MuD expression, which is involved in cell death signaling, was markedly reduced after Q3G treatment.…”

Section: Resultsmentioning

confidence: 99%

Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels

Nile

Shin

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.

show abstract

“…Conversely, some datasets also showed that AP1M2 was poorly expressed in kidney cancer and acute myeloid leukemia compared to normal tissues in the control group. AP1M2, also known as Mu-2, has been shown that Mu-2-related death-inducing gene (MuD) is a 490-amino-acid protein belonging to the medium subunit family of adaptin protein (AP), which can independently induce cancer cell death in association with adhesive protein-mediated endocytosis found in the Mu-2 subunit of the articulation protein [ 21 ]. Therefore, AP1M2 may also possess the function of inducing cancer cell death.…”

Section: Discussionmentioning

confidence: 99%

System Analysis of Adaptor-Related Protein Complex 1 Subunit Mu 2 (AP1M2) on Malignant Tumors: A Pan-Cancer Analysis

Yi¹,

Zhang²,

Shen³

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Objective. To identify new tumor marker genes available for early tumor screening, differentially expressed gene profiles of multiple tumors were compared using Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA) databases. As AP1M2 was highly and differentially expressed in invasive breast carcinoma, the purpose of this study was to explore the association of AP1M2 gene with the survival, immune invasion, and tumor neoantigens of patients on a pan-cancer basis. Methods. The expression and distribution of AP1M2 gene in tumor tissues and the corresponding normal control tissues were analyzed using the pan-cancer databases GTEx, CCLE, and TCGA. Kaplan-Meyer survival plots and proportional hazards model (COX) were employed to evaluate actions of AP1M2 on the clinical prognosis of tumor patients. Subsequently, the association of AP1M2 expression with immune invasion in different tumor types was explored. Simultaneously, the investigation of the interrelationship of AP1M2 and tumor neoantigens of the immune system, unstable microsatellite, DNA repair genes, and DNA methyltransferases were explored, and the mutation frequency of AP1M2 gene in diverse tumors was studied. Several tumor types were analyzed using gene-set enrichment analysis (GSEA). Results. AP1M2 was abundantly expressed in a wide range of cancers, and its expression level was positively correlated with the outcome of tumor victims. Through a study on AP1M2 action on clinical prognosis and immune infiltration in tumor patients, AP1M2 expression in breast-infiltrating carcinoma was found to be highly associated with patients’ overall survival and infiltration levels of macrophages, dendritic cells, T cells (CD4+ and CD8+), and B cells. Also, AP1M2 expression was positively correlated with tumor immune neoantigens and microsatellite instability in breast invasive carcinoma. The effect of AP1M2 on tumors was analyzed by GSEA, and findings demonstrated that AP1M2 expression levels in most tumors influenced the activation of tumor-associated pathways and immune-associated pathways. Conclusions. These findings suggest that AP1M2 expression levels are significantly correlated to patients’ outcomes and levels of immune infiltration in most cancer types, including T cells (CD8+ and CD4+), macrophages, neutrophils, and dendritic cells (DCs), particularly in breast cancer. The results indicate that AP1M2 may influence the tumor environment of invasive breast cancer patients and it may be a target contributing to early screening and treatment for breast cancer, helping improve the efficiency of early screening and overall survival rate in invasive breast cancer patients.

show abstract

The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Cited by 9 publications

References 121 publications

A Personalized Genomics Approach of the Prostate Cancer

A Personalized Genomics Approach of the Prostate Cancer

Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels

System Analysis of Adaptor-Related Protein Complex 1 Subunit Mu 2 (AP1M2) on Malignant Tumors: A Pan-Cancer Analysis

Contact Info

Product

Resources

About