Patent landscape highlighting therapeutic implications of peptides targeting myristoylated alanine-rich protein kinase-C substrate (MARCKS)

Yadav, Vikas; Sharma, Amarish Kumar; Parashar, Gaurav; Parashar, Nidarshana Chaturvedi; Ramniwas, Seema; Jena, Manoj Kumar; Tuli, Hardeep Singh; Yadav, Kiran

doi:10.1080/13543776.2023.2240020

Cited by 7 publications

(1 citation statement)

References 67 publications

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“…ANXA5 served as a bridge between the innate and adaptive immune systems, and the ANXA5-phosphatidylserine axis targeted the tumor environment (TME) and delivered chemotherapeutic agents to the TME to kill tumor cells therein ( Woodward, Faria & Harrison, 2022 ). Data from scRNA in the ascites of STAD patients indicated that MARCKS marked high plasticity and severe survival in STAD ( Huang et al, 2023 ) MARCKS could trigger NF-κB pathway in smoke-relevant lung cancer ( Liu et al, 2021 ), and MARCKS-targeting drug (BIO-11006) has displayed preliminary success in clinical trials of lung diseases ( Yadav et al, 2023 ). Here, our data further showed that inhibition of MARCKS activity markedly reduced the viability of gastric cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Li,

Lu,

et al. 2024

PeerJ

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Background Stomach adenocarcinoma (STAD) exhibits profound tumor heterogeneity and represents a great therapeutic challenge. Single-cell sequencing technology is a powerful tool to identify characteristic cell types. Methods Single-cell sequencing data (scRNA-seq) GSE167297 and bulk RNA-seq data from TCGA, GTEx, GSE26901 and GSE15459 database were included in this study. By downscaling and annotating the cellular data in scRNA-seq, critical cell types in tumor progression were identified by AUCell score. Relevant gene modules were then identified by weighted gene co-expression network analysis (WGCNA). A prognostic scoring system was constructed by identifying prognostic factors in STAD by Least absolute shrinkage and selection operator (LASSO) COX model. The prognosis and model performance in the RiskScore groups were measured by Kaplan-Meier (K-M) curves and Receiver operating characteristic (ROC) curves. Nomogram was drawn based on RiskScore and prognosis-related clinical factors. In addition, we evaluated patient’s feedback on immunotherapy in the RiskScore groups by TIMER, ESTIMATE and TIDE analysis. Finally, the expression levels of prognostic factors were verified in gastric cancer cell lines (MKN7 and MKN28) and human normal gastric mucosal epithelial cells (GES-1), and the effects of prognostic factors on the viability of gastric cancer cells were examined by the CCK8 assay and cell cycle. Results scRNA-seq analysis revealed that 11 cell types were identified, and macrophages exhibited relatively higher AUCell scores and specifically expressed CD14 and FCGR3A. High macrophage scores worsened the prognosis of STAD patients. We intersected the specifically expressed genes in macrophages subgroups (670) and macrophage module genes (2,360) obtained from WGCNA analysis. Among 86 common genes, seven prognostic factors (RGS2, GNAI2, ANXA5, MARCKS, CD36, NRP1 and PDE4A) were identified and composed a RiskScore model. Patients in low Risk group showed a better survival advantage. Nomogram also provided a favorable prediction for survival at 1, 3 and 5 years in STAD patients. Besides, we found positive feedback to immunotherapy in patients with low RiskScore. The expression tendency of the seven prognostic factors in MKN7 and MKN28 was consistent with that in the RNA-seq data in addition to comparison of protein expression levels in the public HPA (The Human Protein Atlas) database. Further functional exploration disclosed that MARCKS was an important prognostic factor in regulating cell viability in STAD. Conclusion This study preliminary uncovered a single cell atlas for STAD patients, and Macrophages relevant gene signature and nomogram displayed favorable immunotherapy and prognostic prediction ability. Collectively, our work provides a new insight into the molecular mechanisms and therapeutic approach for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Li,

Lu,

et al. 2024

PeerJ

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Role for the PIP₂‐binding protein myristoylated alanine‐rich C‐kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease

Albert,

Jahan,

Greenberg

et al. 2024

Journal of Cell Communication and Signaling

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In vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5‐bisphosphate (PIP2) acts as a substrate for phospholipase C (PLC)‐ and phosphoinositol 3‐kinase (PI3K)‐mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP2 are achieved by PIP2‐binding proteins, which act as PIP2 buffers to produce discrete pools of PIP2 that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine‐rich C‐kinase substrate (MARCKS), a PIP2‐binding protein, in cellular signaling and function of VSMCs. The review indicates the possibilities for MARCKS as a therapeutic target for vascular disease involving dysfunctional cell proliferation and migration, endothelial barrier permeability, and vascular contractility such as atherosclerosis, systemic and pulmonary hypertension, and sepsis.

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Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma

Lee,

Chen,

Kenyon

et al. 2024

European Journal of Pharmacology

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Patent landscape highlighting therapeutic implications of peptides targeting myristoylated alanine-rich protein kinase-C substrate (MARCKS)

Cited by 7 publications

References 67 publications

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Role for the PIP₂‐binding protein myristoylated alanine‐rich C‐kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease

Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma

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Patent landscape highlighting therapeutic implications of peptides targeting myristoylated alanine-rich protein kinase-C substrate (MARCKS)

Cited by 7 publications

References 67 publications

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma

Role for the PIP2‐binding protein myristoylated alanine‐rich C‐kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease

Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma

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Role for the PIP₂‐binding protein myristoylated alanine‐rich C‐kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease