DNA replication: Mechanisms and therapeutic interventions for diseases

Song, Haoyun; Shen, Rong; Mahasin, Hamid; Guo, Junming; Wang, De‑Gui

doi:10.1002/mco2.210

Cited by 12 publications

(13 citation statements)

References 382 publications

(843 reference statements)

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“…Mg deficiency is well known to cause inflammation by disturbing the coordination of the innate immune system and the adaptive immune response[14], leading to rapid loss of cell adhesion molecules[46−48]. Alternatively, phospho-signals, serving as the first wave of response to intracellular and extracellular changes, extensively exist during the EMT process[65, 66]. For example, phosphorylation of SNAIL[67], GSK3β[68], and EGFR[69] contributes to the regulation of EMT.…”

Section: Discussionmentioning

confidence: 99%

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Zhang,

Hu,

Liu

et al. 2024

Preprint

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Magnesium (Mg) deficiency is associated with increased risk and malignancy of colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomics and phosphoproteomics indicated that low tumorous Mg content may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which, in turn, enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may offer a promising preventive and therapeutic strategy for CRC.

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Section: Discussionmentioning

confidence: 99%

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Zhang,

Hu,

Liu

et al. 2024

Preprint

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“…PTMs, the breaking or generation of covalent bonds in the protein backbone or amino acid side chains, increase the complexity of the proteome in health and disease 47 . To evaluate the sensitivity of our method for PTM detection, we tested two amino acids with PTMs, P-S and Ac-K (Fig.…”

Section: Discrimination Of Unnatural and Ptm Amino Acidsmentioning

confidence: 99%

Real-time detection of 20 amino acids and discrimination of pathologically relevant peptides with functionalized nanopore

Zhang,

Tang,

Wang

et al. 2024

Nat Methods

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Precise identification and quantification of amino acids is crucial for many biological applications. Here we report a copper(II)-functionalized Mycobacterium smegmatis porin A (MspA) nanopore with the N91H substitution, which enables direct identification of all 20 proteinogenic amino acids when combined with a machine-learning algorithm. The validation accuracy reaches 99.1%, with 30.9% signal recovery. The feasibility of ultrasensitive quantification of amino acids was also demonstrated at the nanomolar range. Furthermore, the capability of this system for real-time analyses of two representative post-translational modifications (PTMs), one unnatural amino acid and ten synthetic peptides using exopeptidases, including clinically relevant peptides associated with Alzheimer’s disease and cancer neoantigens, was demonstrated. Notably, our strategy successfully distinguishes peptides with only one amino acid difference from the hydrolysate and provides the possibility to infer the peptide sequence.

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“…Given that the enzymatic activity is closely associated with anticancer outcome, we examined whether PdMoP nanocrystals feature enzyme-mimicking activities (Figure 2d). [16] Symbolic characteristics of tumor tissue and overexpression of the typical cel-lular antioxidant defense system of GSH have been shown to capture ROS and dilute the anti-tumor impression. [15a] Therefore, the GPx-mimicking activity of PdMoP was examined using a reduced GSH detection kit.…”

Section: Enzyme-mimicking Catalytic Characteristics and Underlying Me...mentioning

confidence: 99%

Engineering Ternary PdMop Nanoenzyme for Enzyodynamic Effect‐Enhanced Ferroptosis and Sonocatalysis‐Enabled Tumor Immunotherapy

Song,

Liu,

Wang

et al. 2023

Adv Funct Materials

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Immunotherapy has become one of the most effective therapeutic modalities for achieving long‐term cancer remission, but the available immunotherapeutic strategies suffer from modest response rates owing to the insufficient immunogenicity of tumor cells. In this work, a nanomedicine strategy for maintaining highly immunogenic tumor cells by inducing cascade‐mediated immunogenic tumor‐cell ferroptosis is proposed and developed. A PdMoP nanoplatform is engineered that not only induces initial immunogenic tumor cell ferroptosis through its multienzyme‐mimicking activities but also accelerates Mo(IV)‐to‐Mo(VI) transition, which aggravates glutathione (GSH) depletion for deactivating glutathione peroxidase 4 (GPX4) enzyme and lead to excessive radical production for promoting p53 expression and reducing SLC7A11, thereby resulting in efficient ferroptosis and apoptosis. Additionally, PdMoP nanoparticles induce the breakdown of hydrogen peroxide into oxygen to alleviate tumor hypoxia, working synergistically with GSH depletion to reverse the immunosuppressive tumor microenvironment. Significant ferroptosis (through the classical p53‐SLC7A11‐GPX4 pathway) is monitored in both in vitro cellular level and in vivo tumor models, achieving effective tumor suppression and elimination. The distinct ultrasound‐enhanced enzyodynamic therapy strategy represents a simple and effective paradigm for treating cancer by nanocatalytic medicine and catalytic biomaterials.

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DNA replication: Mechanisms and therapeutic interventions for diseases

Cited by 12 publications

References 382 publications

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Real-time detection of 20 amino acids and discrimination of pathologically relevant peptides with functionalized nanopore

Engineering Ternary PdMop Nanoenzyme for Enzyodynamic Effect‐Enhanced Ferroptosis and Sonocatalysis‐Enabled Tumor Immunotherapy

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