Identification of Primary and Metastatic Lung Cancer-Related lncRNAs and Potential Targeted Drugs Based on ceRNA Network

Dong, Siyao; Wu, Cheng; Song, Chengyan; Qi, Baocui; Liu, Lu; Xu, Yan

doi:10.3389/fonc.2020.628930

Cited by 8 publications

(7 citation statements)

References 60 publications

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“…The lncRNAs AC037459.2 , AC125807.2 , and ILF3-DT were downregulated across all models of all donor groups post-HDIR. AC037459.2 was previously associated with intracellular signal transduction and likely associated with carcinogenesis ( 47 ). Moreover, AC037459.2 might act jointly with PPP3CC , a neighboring gene, to be involved with osteosarcoma and further cancers by regulating apoptosis and the MAPK signaling pathway, with the need for further research, as the authors themselves stated ( 48 ).…”

Section: Discussionmentioning

confidence: 98%

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls

et al. 2023

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IntroductionLong non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular.MethodsPrimary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function.ResultsAfter irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation).DiscussionFor the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response.

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Section: Discussionmentioning

confidence: 98%

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls

et al. 2023

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“…Considering the importance of the key drivers in autophagy-related ceRNA network [43], a novel ceRNA subnetwork was extracted according to topological properties calculated by the NetworkAnalyzer Tool, including 2 lncRNAs (HOTTIP, LINC00520), 2 DEmiRNAs (miR-125b, miR-181d), and 3 DEmRNAs (BCL2, FKBP1A, and RPS6KB1). HOTTIP, miR-125b, and BCL2 have been studied for their roles in autophagy-related chemoresistance in cancer.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Identification of ZNFs/LINC00520/miR-181d/BCL2 Axis as a Novel Network in Cisplatin-Resistant Lung Adenocarcinoma Cells

Xu¹,

Guo²,

Guo³

et al. 2023

AJMB

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Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, therefore, novel strategies to reverse chemoresistance by regulating autophagy are desperately needed. Methods: The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between A549 and A549/DDP cell lines were identified using the limma package in R, after gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. By combining Autophagy-Related Genes (ARGs) from Human Autophagy Database (HADb), the interactions lncRNA-miRNAs and the interactions miRNAs-mRNAs respectively predicted by miRcode and miRDB/Targetscan database, the autophagy-related ceRNA network was constructed. Then, extraction of ceRNA subnetwork and Cox regression analyses were performed. A prognosis-related ceRNA subnetwork was constructed, and the upstream Transcription Factors (TFs) regulating lncRNAs were predicted by the JASPAR database. Finally, the expression patterns of candidate

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“…Lung cancer metastasis is closely related to poor prognosis and survival outcomes in patients and is largely a result of alterations in gene expression, structure, and function [28]. As such, we investigated the correlations between significantly dysregulated eRNAs and cancer metastasis.…”

Section: Clinical Significance Of Smoking Modulated Ernas On Lusc Pathogenesis and Tumor Developmentmentioning

confidence: 99%

Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma

Tsai

Saad

Magesh

et al. 2021

Cancers

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Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.

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Identification of Primary and Metastatic Lung Cancer-Related lncRNAs and Potential Targeted Drugs Based on ceRNA Network

Cited by 8 publications

References 60 publications

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls

Bioinformatics Identification of ZNFs/LINC00520/miR-181d/BCL2 Axis as a Novel Network in Cisplatin-Resistant Lung Adenocarcinoma Cells

Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma

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