Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates
BackgroundThe competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.904865/full |
| _version_ | 1817979352465276928 |
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| author | Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Jing Gao Qin Yu Min Zhang Wei-Dong Hu |
| author_facet | Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Jing Gao Qin Yu Min Zhang Wei-Dong Hu |
| author_sort | Xiao-Jun Wang |
| collection | DOAJ |
| description | BackgroundThe competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC.MethodWe determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC.ResultsThe multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways.ConclusionsWe identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC. |
| first_indexed | 2024-04-13T22:41:48Z |
| format | Article |
| id | doaj.art-5daf31e18f48420b913031c79de1fe6f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:41:48Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5daf31e18f48420b913031c79de1fe6f2022-12-22T02:26:35ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.904865904865Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug CandidatesXiao-Jun Wang0Xiao-Jun Wang1Jing Gao2Jing Gao3Jing Gao4Jing Gao5Qin Yu6Min Zhang7Wei-Dong Hu8Department of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaRespiratory Medicine Unit, Department of Medicine, Karolinska Institute, Stockholm, SwedenDepartment of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Pathology, Gansu Provincial Hospital, Lanzhou, ChinaDepartment of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, ChinaBackgroundThe competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC.MethodWe determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC.ResultsThe multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways.ConclusionsWe identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC.https://www.frontiersin.org/articles/10.3389/fonc.2022.904865/fullsmall cell lung cancer (SCLC)multi-omics integrationcompeting endogenous RNA (ceRNA)long noncoding RNA (lncRNA)circular RNA (circRNA)microRNA (miRNA) |
| spellingShingle | Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Jing Gao Qin Yu Min Zhang Wei-Dong Hu Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates Frontiers in Oncology small cell lung cancer (SCLC) multi-omics integration competing endogenous RNA (ceRNA) long noncoding RNA (lncRNA) circular RNA (circRNA) microRNA (miRNA) |
| title | Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates |
| title_full | Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates |
| title_fullStr | Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates |
| title_full_unstemmed | Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates |
| title_short | Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates |
| title_sort | multi omics integration based prioritisation of competing endogenous rna regulation networks in small cell lung cancer molecular characteristics and drug candidates |
| topic | small cell lung cancer (SCLC) multi-omics integration competing endogenous RNA (ceRNA) long noncoding RNA (lncRNA) circular RNA (circRNA) microRNA (miRNA) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.904865/full |
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