Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

Gulhane, Pooja; Singh, Shailza

doi:10.1016/j.tranon.2023.101673

Cited by 3 publications

(1 citation statement)

References 163 publications

(162 reference statements)

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“…Despite great advances that have been made in targeted therapy, the 5-year survival rate is relatively low, and drug resistance inevitably occurs during treatment. Subsequently, studies focused on epigenetic modification were gradually carried out, such as phosphorylation, methylation, and glycosylation 2 . Post-translational modifications (PTMs) occur in more than 50% of proteins and directly influence the function of proteins in many fundamental biological processes.…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma

Wang,

Hou,

et al. 2024

Sci Rep

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There has been increasing interest in the role of epigenetic modification in cancers recently. Among the various modifications, sialylation has emerged as a dominant subtype implicated in tumor progression, metastasis, immune evasion, and chemoresistance. The prognostic significance of sialylation-related molecules has been demonstrated in colorectal cancer. However, the potential roles and regulatory mechanisms of sialylation in lung adenocarcinoma (LUAD) have not been thoroughly investigated. Through Pearson correlation, univariate Cox hazards proportional regression, and random survival forest model analyses, we identified several prognostic long non-coding RNAs (lncRNAs) associated with aberrant sialylation and tumor progression, including LINC00857, LINC00968, LINC00663, and ITGA9-AS1. Based on the signatures of four lncRNAs, we classified patients into two clusters with different landscapes using a non-negative matrix factorization approach. Collectively, patients in Cluster 1 (C1) exhibited worse prognoses than those in Cluster 2 (C2), as well as heavier tumor mutation burden. Functional enrichment analysis showed the enrichment of several pro-tumor pathways in C1, differing from the upregulated Longevity and programmed cell death pathways in C2. Moreover, we profiled immune infiltration levels of important immune cell lineages in two subgroups using MCPcounter scores and single sample gene set enrichment analysis scores, revealing a relatively immunosuppressive microenvironment in C1. Risk analysis indicated that LINC00857 may serve as a pro-tumor regulator, while the other three lncRNAs may be protective contributors. Consistently, we observed upregulated LINC00857 in C1, whereas increased expressive levels of LINC00968, LINC00663, and ITGA9-AS1 were observed in C2. Finally, drug sensitivity analysis suggested that patients in the two groups may benefit from different therapeutic strategies, contributing to precise treatment in LUAD. By integrating multi-omics data, we identified four core sialylation-related lncRNAs and successfully established a prognostic model to distinguish patients with different characterizations. These findings may provide some insights into the underlying mechanism of sialylation, and offer a new stratification way as well as clinical guidance in LUAD.

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Section: Introductionmentioning

confidence: 99%

The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma

Wang,

Hou,

et al. 2024

Sci Rep

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The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives

Chen,

Jiang,

Yang

et al. 2023

International Journal of Biological Macromolecules

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PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells

Luo,

Hu,

Tang

et al. 2024

CCDT

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Background: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. Objective: To explore the role of palmitoyl protein thioesterase 1 (PPT1) in OSCC. Methods: Differentially Expressed Genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients’clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments, including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate the gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. Results: A total of 555 DEGs were obtained, and topological analysis revealed that the PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibiting the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). conclusion: PPT1 inhibits ferroptosis and promotes the growth of OSCC cells. PPT1 may be a potential therapeutic target for OSCC.

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Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

Cited by 3 publications

References 163 publications

The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma

The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma

The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives

PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells

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