Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Abstract

Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

Revealing a potential necroptosis‐related axis (RP11‐138A9.1/hsa‐miR‐98‐5p/ZBP1) in periodontitis by construction of the ceRNA network

“…61 Tan et al constructed a novel glycolysis-related LINC02432/hsa-miR-98-5p/HK2 ceRNA network that was markedly associated with ferroptosis, immune infiltration, and drug sensitivity. 62 To our best knowledge, no study has revealed the pathogenesis of lncRNA RP11-138A9.1, RP11-96D1.11, and RP4-773 N10.4 in periodontitis yet. Recent investigations have gradually demonstrated that the novel lncRNA profiles of periodontitis patients are significantly different from that of healthy controls, and some new potential mechanisms and roles of lncRNA in periodontitis have been gradually discovered by microarray and genome-wide sequencing.…”

“…IL‐10 was identified as a Th2 cytokine that downregulates inflammatory cytokines produced by Th1 61 . Tan et al constructed a novel glycolysis‐related LINC02432/hsa‐miR‐98‐5p/HK2 ceRNA network that was markedly associated with ferroptosis, immune infiltration, and drug sensitivity 62 . To our best knowledge, no study has revealed the pathogenesis of lncRNA RP11‐138A9.1, RP11‐96D1.11, and RP4‐773 N10.4 in periodontitis yet.…”

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer

“…Our selective approach contrasts with that of other previously published works on related matters, and we hypothesize that it is of higher clinical translational relevance. Previous studies aimed at developing miRNA-based PC diagnostics are technologically limited, as they did not integrate the real-world datasets [ 25 – 27 ] or they relied on somewhat outdated computational algorithms [ 28 – 32 ]. Moreover, others have suggested a circulating three microRNA panel (miR-642b, miR-885-5p, and miR-22) for blood-based detection of PC [ 33 ].…”

Glycolysis: an emerging regulator of osteoarthritis

“…Inhibition of sirtuins6 in pancreatic cancer (PC) can lead to ferroptosis in cells as well as promote LA production and enhance HK2 and LDHA ( 215 ). Besides, the LINC02432/Hsa-miR-98–5p/HK2 axis associated with glycolysis regulates the ferroptosis pathway in PC ( 216 ). Recombinant pyruvate dehydrogenase kinase isozyme 4 mediated glycolysis in liver fibrosis affects the susceptibility of hepatic stellate cells to ferroptosis ( 217 ).…”