Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Liu, Zhaoping; Wang, Yanyan; Xu, Zhenru; Yuan, Shunling; Ou, Yanglin; Luo, Zeyu; Feng, Wen; Liu, Jing; Zhang, Ji

doi:10.7717/peerj.11429

Cited by 4 publications

(4 citation statements)

References 56 publications

(61 reference statements)

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“…This agreed with the findings of this study. In addition, earlier research (51) suggested that LINC01515 exerted a key function in the drug resistance of leukemia cells. However, in our study, LINC01515 was identified as the CRLs of HCC, while Liu reported lncRNArelated immunity.…”

Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma

et al. 2022

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Intratumoral copper levels are closely associated with immune escape from diverse cancers. Cuproptosis-related lncRNAs (CRLs), however, have an unclear relationship with hepatocellular carcinoma (HCC). Gene expression data from 51 normal tissues and 373 liver cancer tissues from the Cancer Genome Atlas (TCGA) database were collected and analyzed. To identify CRLs, we employed differentially expressed protein-coding genes (DE-PCGs)/ lncRNAs (DE-lncRNAs) analysis, Kaplan-Meier (K-M) analysis, and univariate regression. By univariate and Lasso Cox regression analyses, we screened 10 prognosis-related lncRNAs. Subsequently, five CRLs were identified by multivariable Cox regression analysis to construct the prognosis model. This feature is an independent prognostic indicator to forecast overall survival. According to Gene Set Variation Analysis (GSVA) and Gene Ontology (GO), both immune-related biological processes (BPS) and pathways have CRL participation. In addition, we found that the characteristics of CRLs were associated with the expression of the tumor microenvironment (TME) and crucial immune checkpoints. CRLs could predict the clinical response to immunotherapy based on the studies of tumor immune dysfunction and rejection (TIDE) analysis. Additionally, it was verified that tumor mutational burden survival and prognosis were greatly different between high-risk and low-risk groups. Finally, we screened potential sensitive drugs for HCC. In conclusion, this study provides insight into the TME status in patients with HCC and lays a basis for immunotherapy and the selection of sensitive drugs.

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Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma

et al. 2022

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“…It promotes imatinib resistance in human gastrointestinal stromal tumors ( Yan et al, 2019 ). Its inhibition could increase the sensitivity of doxorubicin in MDR-CML cells ( Liu et al, 2021b ). In this study, we predicted that CCDC26 could be associated with lung cancer in dataset 1.…”

Section: Resultsmentioning

confidence: 99%

Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM

Su,

Lu,

et al. 2023

Front. Genet.

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Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tumor and is mainly involved in childhood patients. Identification of new biomarkers for these two diseases can significantly promote their diagnosis and therapy. However, in vivo experiments to discover potential biomarkers are costly and laborious. Consequently, artificial intelligence technologies, especially machine learning methods, provide a powerful avenue to find new biomarkers for various diseases.Methods: We developed a machine learning-based method named LDAenDL to detect potential long noncoding RNA (lncRNA) biomarkers for lung cancer and neuroblastoma using an ensemble of a deep neural network and LightGBM. LDAenDL first computes the Gaussian kernel similarity and functional similarity of lncRNAs and the Gaussian kernel similarity and semantic similarity of diseases to obtain their similar networks. Next, LDAenDL combines a graph convolutional network, graph attention network, and convolutional neural network to learn the biological features of the lncRNAs and diseases based on their similarity networks. Third, these features are concatenated and fed to an ensemble model composed of a deep neural network and LightGBM to find new lncRNA–disease associations (LDAs). Finally, the proposed LDAenDL method is applied to identify possible lncRNA biomarkers associated with lung cancer and neuroblastoma.Results: The experimental results show that LDAenDL computed the best AUCs of 0.8701, 107 0.8953, and 0.9110 under cross-validation on lncRNAs, diseases, and lncRNA‐disease pairs on Dataset 1, respectively, and 0.9490, 0.9157, and 0.9708 on Dataset 2, respectively. Furthermore, AUPRs of 0.8903, 0.9061, and 0.9166 under three cross‐validations were obtained on Dataset 1, and 0.9582, 0.9122, and 0.9743 on Dataset 2. The results demonstrate that LDAenDL significantly outperformed the other four classical LDA prediction methods (i.e., SDLDA, LDNFSGB, IPCAF, and LDASR). Case studies demonstrate that CCDC26 and IFNG-AS1 may be new biomarkers of lung cancer, SNHG3 may associate with PDL1 for lung cancer, and HOTAIR and BDNF-AS may be potential biomarkers of neuroblastoma.Conclusion: We hope that the proposed LDAenDL method can help the development of targeted therapies for these two diseases.

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“…Studies have reported that ceRNA and drug target networks can provide effective and innovative therapeutic strategies for diseases. For example, analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR (Liu et al, 2021), and ceRNA networks provide potential biomarkers and therapeutic targets for colorectal cancer (Wang et al, 2019), and in SARS-CoV-2 infection (COVID-19) (Arora et al, 2020). Therefore, it can provide novel and effective targets for the development of innovative therapeutic strategies against VV.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

Liu²,

Liu³

et al. 2022

Front. Genet.

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Background: Patients with Varicose veins (VV) show no obvious symptoms in the early stages, and it is a common and frequent clinical condition. DNA methylation plays a key role in VV by regulating gene expression. However, the molecular mechanism underlying methylation regulation in VV remains unclear.Methods: The mRNA and methylation data of VV and normal samples were obtained from the Gene Expression Omnibus (GEO) database. Methylation-Regulated Genes (MRGs) between VV and normal samples were crossed with VV-associated genes (VVGs) obtained by weighted gene co-expression network analysis (WGCNA) to obtain VV-associated MRGs (VV-MRGs). Their ability to predict disease was assessed using receiver operating characteristic (ROC) curves. Biomarkers were then screened using a random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). Next, gene set enrichment analysis (GSEA) was performed to explore the functions of biomarkers. Furthermore, we also predicted their drug targets, and constructed a competing endogenous RNAs (ceRNA) network and a drug target network. Finally, we verified their mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR).Results: Total three VV-MRGs, namely Wnt1-inducible signaling pathway protein 2 (WISP2), Cysteine-rich intestinal protein 1 (CRIP1), and Odd-skipped related 1 (OSR1) were identified by VVGs and MRGs overlapping. The area under the curves (AUCs) of the ROC curves for these three VV-MRGs were greater than 0.8. RF was confirmed as the optimal diagnostic model, and WISP2, CRIP1, and OSR1 were regarded as biomarkers. GSEA showed that WISP2, CRIP1, and OSR1 were associated with oxidative phosphorylation, extracellular matrix (ECM), and respiratory system functions. Furthermore, we found that lncRNA MIR17HG can regulate OSR1 by binding to hsa-miR-21-5p and that PAX2 might treat VV by targeting OSR1. Finally, qRT-PCR results showed that the mRNA expression of the three genes was consistent with the results of the datasets.Conclusion: This study identified WISP2, CRIP1, and OSR1 as biomarkers of VV through comprehensive bioinformatics analysis, and preliminary explored the DNA methylation-related molecular mechanism in VV, which might be important for VV diagnosis and exploration of potential molecular mechanisms.

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Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Cited by 4 publications

References 56 publications

A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma

A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma

Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

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