WT1-AS/IGF2BP2 Axis Is a Potential Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma According to ceRNA Network Comprehensive Analysis Combined with Experiments

Jia, Mingxi; Shi, Yi; Xie, Yang; Li, Wen; Deng, Jing; Fu, Da; Bai, Jie; Ma, Yu‐Shui; Zuberi, Zavuga; Li, Juan; Li, Zheng

doi:10.3390/cells11010025

Cited by 7 publications

(6 citation statements)

References 46 publications

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“…Imbalances of lncRNA are also associated with the development of many diseases and complications, such as premature preterm rupture of membrane, autism spectrum disorders, and cancer [ 11 , 12 , 13 , 14 ]. MicroRNAs (miRNAs) target and induce translation inhibition or degradation of mRNA to control gene expression and regulate biological processes [ 15 , 16 ]. They play an important role in tumorigenesis and metastasis by targeting multiple oncogenic signaling pathways such as Notch, Wnt/β-catenin, JAKs/STAT3, PI3K/AKT and NF-κB pathway [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

Feng

et al. 2022

Cells

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Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

Feng

et al. 2022

Cells

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“…Genes encoding the IGF2BP family, including IGF2BP 1, IGF2BP2 and IGF2BP3, were widely overexpressed and associated with poor prognosis in a variety of human malignancies as RNA stabilizers 46 . For example, Jia et al 47 found high transcription level of IGF2BP2 and the association with poor prognosis in LUAD. Further, they suggested that IGF2BP2 could exert its oncogenic effect through the competitive action of WT1-AS with miR-200a based on a c-Myc-associated ceRNA network analysis.…”

Section: Discussionmentioning

confidence: 99%

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis

Zhang,

Hu,

Shi

et al. 2023

Int. J. Med. Sci.

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Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

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“…The ceRNA network was constructed according to the method described previously [ 27 ]. Briefly: (1) Prediction of potential miRNAs for DElncRNA targeting through the mircode database ( , accessed on 20 March 2022); (2) miRDB databases ( , accessed on 20 March 2022) and the Targetscan database ( , accessed on 20 March 2022) were used to identify the downstream targets (mRNAs) of miRNAs; (3) The lncRNA-miRNA-mRNA ceRNA network was visualized by Cytoscape v3.7.0.…”

Section: Methodsmentioning

confidence: 99%

“…Lung adenocarcinoma cell lines (A549, PC-9 and H1299) and the normal bronchial epithelial cell line (BEAS-2B) were cultured in 1640 medium (Thermo Fisher Scientific, Waltham, MA, USA) containing 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, MA, USA), 100 U/mL streptomycin and 100 U/mL penicillin (Sangon Biotech, Shanghai, China) at 37 °C and 5% CO 2 . RNA was extracted according to the previous experimental method and detected by RT-PCR [ 27 ]. The primer sequences were as follows:…”

Section: Methodsmentioning

confidence: 99%

Identification of EGFR-Related LINC00460/mir-338-3p/MCM4 Regulatory Axis as Diagnostic and Prognostic Biomarker of Lung Adenocarcinoma Based on Comprehensive Bioinformatics Analysis and Experimental Validation

Jia

Feng²,

Cao³

et al. 2022

Cancers

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Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, the regulation of the EGFR by competing endogenous RNAs (ceRNAs) has been extensively studied and significant progress has been made. Therefore, we aim to find new targets for the diagnosis and treatment of LUAD by analyzing the EGFR-related ceRNA network in LUAD and expect to address the problem of EGFR resistance. Methods: We identified differentially expressed lncRNAs, miRNAs and mRNAs closely associated with the EGFR by analyzing transcriptome data from LUAD samples. Comprehensive bioinformatics analysis strongly suggests that the LINC00460—mir-338-3p—MCM4 ceRNA network plays an important role in the diagnosis and prognosis of LUAD. The effects of different patterns of the LINC00460/MCM4 axis on the overall survival of patients with LUAD were analyzed by a polygene regulation model. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. The functional enrichment analysis and targeted drug prediction of the MCM4 gene were performed. Results: Survival analysis indicated that high expressions of LINC00460 and MCM4 predict a shorter survival period for patients. Univariate and multivariate regression analyses demonstrated that higher expressions of LINC00460 and MCM4 were significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation)—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients (p = 0.0093). RT-PCR and immunohistochemical experiments confirmed our analytical results. In addition, the functional enrichment analysis indicated that MCM4-related genes were mainly enriched in the cell cycle and cell division. A functional association network analysis showed that MCM4 was closely related to the EGFR. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes. Conclusions: In summary, the LINC00460/MCM4 axis can be used as a potential new perspective for targeting EGFR genes in precision medicine and is expected to serve as a diagnostic, prognostic and drug target for LUAD.

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WT1-AS/IGF2BP2 Axis Is a Potential Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma According to ceRNA Network Comprehensive Analysis Combined with Experiments

Cited by 7 publications

References 46 publications

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis

Identification of EGFR-Related LINC00460/mir-338-3p/MCM4 Regulatory Axis as Diagnostic and Prognostic Biomarker of Lung Adenocarcinoma Based on Comprehensive Bioinformatics Analysis and Experimental Validation

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