Identification of the KCNQ1OT1/ miR-378a-3p/ RBMS1 Axis as a Novel Prognostic Biomarker Associated With Immune Cell Infiltration in Gastric Cancer

Abstract

Background: Gastric cancer (GC) is the second leading cause of cancer-related mortality and the fifth most common cancer worldwide. However, the underlying mechanisms of competitive endogenous RNAs (ceRNAs) in GC are unclear. This study aimed to construct a ceRNA regulation network in correlation with prognosis and explore a prognostic model associated with GC.Methods: In this study, 1,040 cases of GC were obtained from TCGA and GEO datasets. To identify potential prognostic signature associated with GC, Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression were employed. The prognostic value of the signature was validated in the GEO84437 training set, GEO84437 test set, GEO15459 set, and TCGA-STAD. Based on the public databases, TargetScan and starBase, an mRNA-miRNA-lncRNA regulatory network was constructed, and hub genes were identified using the CytoHubba plugin. Furthermore, the clinical outcomes, immune cell infiltration, genetic variants, methylation, and somatic copy number alteration (sCNA) associated with the ceRNA network were derived using bioinformatics methods.Results: A total of 234 prognostic genes were identified. GO and GSEA revealed that the biological pathways and modules related to immune response and fibroblasts were considerably enriched in GC. A nomogram was generated to provide accurate prognostic outcomes and individualized risk estimates, which were validated in the training, test dataset, and two independent validation datasets. Thereafter, an mRNA-miRNA-lncRNA regulatory network containing 4 mRNAs, 22 miRNAs, 201 lncRNAs was constructed. The KCNQ1OT1/hsa-miR-378a-3p/RBMS1 ceRNA network associated with the prognosis was obtained by hub gene analysis and correlation analysis. Importantly, we found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may play a vital role in the diagnosis and prognosis of GC patients based on Cox regression analyses. Furthermore, our findings demonstrated that mutations and sCNA of the KCNQ1OT1/miR-378a-3p/RBMS1 axis were associated with increased immune infiltration, while the abnormal upregulation of the axis was primarily a result of hypomethylation.Conclusion: Our findings suggest that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and therapeutic target for GC. Moreover, such findings provide insights into the molecular mechanisms of GC pathogenesis.

Glycyrrhizic acid protects against temporal lobe epilepsy in young rats by regulating neuronal ferroptosis through the miR‐194‐5p/PTGS2 axis

“…Our findings demonstrated that GA treatment at any dose level led to significant reductions in the score, frequency, and duration of epileptic seizures in TLE young rats, and exhibited the best efficacy at the dosage of 60 mg/kg. A prior study suggested that GA is absorbed into the blood, which then crosses the blood–brain barrier (BBB) to reach the brain and exert its protective effects, which is a possible explanation for our findings 23 . Additionally, evidence has come to light indicating the presence of ferroptosis in the hippocampus after TLE 6 .…”

“…A prior study suggested that GA is absorbed into the blood, which then crosses the bloodbrain barrier (BBB) to reach the brain and exert its protective effects, which is a possible explanation for our findings. 23 Additionally, evidence has come to light indicating the presence of ferroptosis in the hippocampus after TLE. 6 Moreover, GA can elicit strong neuroprotective effects in rodent models of vascular dementia via inhibition of oxidative stress and diminishing the release of cytochrome-c. 30 Wang Y et al highlighted that GA can attenuate the degree of ferroptosis in acute liver failure through the inhibition of oxidative stress.…”

“…Luciferase activity was measured with the help of dual‐luciferase reporter assay kits (Beyotime) under the manufacturer's instructions. First, the potential binding site of miR‐194‐5p and PTGS2 was predicted using the TargetScan version 7.2 database (http://www.targetscan.org/), 23 and the complementary binding sequences and mutant (MUT) sequences of miR‐194‐5p and PTGS2 were amplified based on the prediction results, and subsequently cloned onto the pmir‐GLO luciferase vectors (Promega, Madison, WI, USA) to construct the wild‐type (WT) plasmid PTGS2‐WT and corresponding mutant plasmid PTGS2‐MUT. Next, miR‐194‐5p mimic or mimic NC and corresponding plasmids were co‐transfected into H293T cells (Xuran Biotechnology, Shanghai, China) using the Lipofectamine 2000 reagent (Invitrogen).…”

Identification and validation of a novel angiogenesis-related gene signature for predicting prognosis in gastric adenocarcinoma

“…For example, Ting Yue et al. found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and provide insights into the molecular mechanisms of GC pathogenesis ( 28 ). LncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for GC ( 29 ).…”

“…High-throughput sequencing analysis has revealed many deregulated lncRNAs in human cancers, and abnormal expression of lncRNAs is related to tumor recurrence and metastasis (10, 26, 27). For example, Ting Yue et al found that the KCNQ1OT1/miR-378a-3p/ RBMS1 axis may be a potential prognostic biomarker and provide insights into the molecular mechanisms of GC pathogenesis (28). LncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for GC (29).…”