Identifying an lncRNA-Related ceRNA Network to Reveal Novel Targets for a Cutaneous Squamous Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34068010", "kind": "science-record", "revision": 7, "content_hash": "sha256:a8a187393c26ba1c3725032a31678b545d6c502520b172797e80ff7b5c38e5bb", "created_at": "2026-11-01T15:41:37Z", "updated_at": "2026-11-01T22:03:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identifying an lncRNA-Related ceRNA Network to Reveal Novel Targets for a Cutaneous Squamous Cell Carcinoma.", "doi": "10.3390/biology10050432", "pmid": "34068010", "authors": ["Yaqin Xu", "Yingying Dong", "Yunhua Deng", "Qianrong Qi", "Mi Wu", "Hongmei Liang", "Qiuyun She", "Qing Guo"], "journal": "Biology", "year": 2021, "abstract": "A cutaneous squamous cell carcinoma (cSCC) derived from keratinocytes is the second most common cause of non-melanoma skin cancer. The accumulation of the mutational burden of genes and cellular DNA damage caused by the risk factors (e.g., exposure to ultraviolet radiation) contribute to the aberrant proliferation of keratinocytes and the formation of a cSCC. A cSCC encompasses a spectrum of diseases that range from recursor actinic keratosis (AK) and squamous cell carcinoma (SCC) in situ (SCCIS) to invasive cSCCs and further metastatic SCCs. Emerging evidence has revealed that lncRNAs are involved in the biological process of a cSCC. According to the ceRNA regulatory theory, lncRNAs act as natural miRNA sponges and interact with miRNA response elements, thereby regulating the mRNA expression of their down-stream targets. This study was designed to search for the potential lncRNAs that may become potential therapeutic targets or biomarkers of a cSCC. Considering the spirit of the study to be adequately justified, we collected microarray-based datasets of 19 cSCC tissues and 12 normal skin samples from the GEO database (GSE42677 and GSE45164). After screening the differentially expressed genes via a limma package, we identified 24 differentially expressed lncRNAs (DElncRNAs) and 3221 differentially expressed mRNAs (DEmRNAs). The miRcode, miRTarBase, miRDB and TargetScan databases were used to predict miRNAs that could interact with DElncRNAs and DEmRNAs. A total of 137 miRNA-lncRNA and 221 miRNA-mRNA pairs were retained in the ceRNA network, consisting of 31 miRNAs, 11 DElncRNAs and 155 DEmRNAs. For the functional analysis, the top enriched biological process was enhancer sequence-specific DNA binding in Gene Ontology (GO) terms. The FoxO signaling pathway, autophagy and cellular senescence were the top enrichment terms based on a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The combination of a STRING tool and Cytoscape software (plug-in MCODE) identified five core mRNAs and built a core mRNA-associated ceRNA network. The expression for five identified core mRNAs and their related nine lncRNAs was validated using the external dataset GSE7553. Finally, one lncRNA HLA-F-AS1 and three mRNAs named AGO4, E2F1 and CCND1 were validated with the same expression patterns. We speculate that lncRNA HLA-F-AS1 may sponge miR-17-5p or miR-20b-5p to regulate the expression of CCND1 and E2F1 in the cSCC. The present study may provide potential diagnostic and therapeutic targets for cSCC patients.", "claims": [{"id": "claim-data-access", "statement": "Data were obtained from the GEO database and are available at: www.ncbi.nlm.nih.gov/geo (accessed on 24 August 2020) with the permission of the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34068010", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "Data were obtained from the GEO database and are available at: www.ncbi.nlm.nih.gov/geo (accessed on 24 August 2020) with the permission of the GEO database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34068010"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Discussion", "row_count": 7, "column_count": 3}, "table": {"label": "Table 1", "caption": "Summary of the roles and mechanisms of discussed lncRNAs and miRNAs in the pathogenesis of cancers.", "rows": [["LncRNA/miRNA", "Gene Targets", "Mechanisms in Cancers"], ["HLA-F-AS1", "MiR-541-3p", "Promotion of cell proliferation and stemness in vitro and tumor growth in vivo by the miR-541-3p/TRABD axis in triple-negative breast cancer [50].Promotion of cell proliferation, migration and invasion and repression of apoptosis in vitro via the miR-330-3p/ PFN1 axis in colorectal cancer [48]."], ["MiR-330-3p"], ["MiR-17-5p", "3′ UTR of CCND1", "Repression of the CCND1 protein expression via sponging with the CCND1 3′-UTR region in a lung cancer cell [46].Promotion of cell growth, proliferation, migration and colony formation in vitro in a non-metastatic hepatocellular carcinoma by regulating E2F1 expression [52]."], ["E2F1"], ["MiR-20b-5p", "3′ UTR of CCND1", "Promotion of myoblast differentiation and repression of myoblast proliferation by regulating E2F1 expression [47].Promotion of cell proliferation, G1/S transition and DNA synthesis by downregulating CCND1 and E2F1 expression in multipotent stromal cells [53].Promotion of cell migration and proliferation and repression of apoptosis of breast cancer stem cells and promoting tumor growth in vivo by bidirectionally regulating the protein levels of CCND1 and E2F1 in breast cancer [54].Inhibition of the cell cycle, migration and invasion in vitro and the tumorigenesis in vivo by negatively regulating CCND1 in colon cancer [55]."], ["3′ UTR of E2F1"]], "row_count": 7, "column_count": 3, "numeric_cells": 10, "header_rows": 1, "locator": "section[15]/table-wrap[1]#biology-10-00432-t001"}}, {"id": "asset:table:pmid:34068010:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7cfabee83b3fb5ba028432cfdde690aa5d839b135ed430f955104ca7d5fb8a17", "bytes": 1863, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#array1", "version": null, "note": null, "structure": {"pmcid": "PMC8152267", "section_index": 17, "section_title": "Abbreviations", "row_count": 45, "column_count": 2}, "table": {"label": null, "caption": null, "rows": [["SCC", "Squamous Cell Carcinoma"], ["cSCC", "Cutaneous Squamous Cell Carcinoma"], ["SCCIS", "Squamous Cell Carcinoma (SCC) In Situ"], ["NcRNAs", "Non-Coding RNAs"], ["LncRNAs", "Long Non-Coding RNAs"], ["MiRNAs", "MicroRNAs"], ["CeRNAs", "Competing Endogenous RNAs"], ["NS", "Normal Skin"], ["DEGs", "Differentially Expressed Genes"], ["DElncRNAs", "Differentially Expressed LncRNAs"], ["DEmRNAs", "Differentially Expressed MRNAs"], ["GEO", "Gene Expression Omnibus"], ["GO", "Gene Ontology"], ["BP", "Biological Processes"], ["KEGG", "Kyoto Encyclopedia of Genes and Genomes"], ["STRING", "Search Tool for the Retrieval of Interacting Genes"], ["MCODE", "Molecular Complex Detection"], ["FDR", "False Discovery Rate"], ["FC", "Fold Change"], ["PCA", "Principal Component Analysis"], ["PCC", "Pearson’s Correlation Coefficient"], ["CDC20", "Cell Division Cycle 20"], ["EGFR", "Epidermal Growth Factor Receptor"], ["PRAF2", "Prenylated Rab Acceptor 1 Domain Family Member 2"], ["FoxO", "Forkhead box O"], ["HLA-F-AS1", "HLA-F Antisense RNA 1"], ["CCND1", "Cyclin D1"], ["E2F1", "E2F Transcription Factor 1"], ["AGO4", "Argonaute-4"], ["LAD", "Lung Adenocarcinoma"], ["CRC", "Colorectal Cancer"], ["PFN1", "Profilin 1"], ["ESCC", "Esophageal Squamous Cell Carcinoma"], ["TSCC", "Tongue Squamous Cell Carcinoma Progression"], ["LSCC", "Laryngeal Squamous Cell Carcinoma"], ["HNSCC", "Head and Neck Squamous Cell Carcinoma"], ["OSCC", "Oral Squamous Cell Carcinoma"], ["RdDM", "RNA-Dependent DNA Methylation"], ["DNMT3A", "DNA Methyltransferase 3A"], ["GBM", "Glioblastoma Multiforme"], ["AK", "Actinic Keratosis"], ["NEAT1", "Nuclear Paraspeckle 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