IGF-1-enhanced miR-513a-5p signaling desensitizes glioma cells to temozolomide by targeting the NEDD4L-inhibited Wnt/β-catenin pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31805126", "kind": "science-record", "revision": 7, "content_hash": "sha256:9da2ee69fdf0fe73a1eb9fb7790f894cd2bd503bdc87346d47bae9ae5aa222dd", "created_at": "2026-11-01T15:40:53Z", "updated_at": "2026-11-01T21:22:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "IGF-1-enhanced miR-513a-5p signaling desensitizes glioma cells to temozolomide by targeting the NEDD4L-inhibited Wnt/β-catenin pathway.", "doi": "10.1371/journal.pone.0225913", "pmid": "31805126", "authors": ["Ku-Chung Chen", "Peng-Hsu Chen", "Kuo-Hao Ho", "Chwen-Ming Shih", "Chih-Ming Chou", "Chia-Hsiung Cheng", "Chin-Cheng Lee"], "journal": "PloS one", "year": 2019, "abstract": "Temozolomide (TMZ) is a first-line alkylating agent for glioblastoma multiforme (GBM). Clarifying the mechanisms inducing TMZ insensitivity may be helpful in improving its therapeutic effectiveness against GBM. Insulin-like growth factor (IGF)-1 signaling and micro (mi)RNAs are relevant in mediating GBM progression. However, their roles in desensitizing GBM cells to TMZ are still unclear. We aimed to identify IGF-1-mediated miRNA regulatory networks that elicit TMZ insensitivity for GBM. IGF-1 treatment attenuated TMZ cytotoxicity via WNT/β-catenin signaling, but did not influence glioma cell growth. By miRNA array analyses, 93 upregulated and 148 downregulated miRNAs were identified in IGF-1-treated glioma cells. miR-513a-5p from the miR-513a-2 gene locus was upregulated by IGF-1-mediated phosphoinositide 3-kinase (PI3K) signaling. Its elevated levels were also observed in gliomas versus normal cells, in array data of The Cancer Genome Atlas (TCGA), and the GSE61710, GSE37366, and GSE41032 datasets. In addition, lower levels of neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin protein ligase that inhibits WNT signaling, were found in gliomas by analyzing cells, arrays, and RNA sequencing data of TCGA glioma patients. Furthermore, a negative correlation was identified between miR-513a-5p and NEDD4L in glioma. NEDD4L was also validated as a direct target gene of miR-513a-5p, and it was reduced by IGF-1 treatment. Overexpression of NEDD4L inhibited glioma cell viability and reversed IGF-1-repressed TMZ cytotoxicity. In contrast, miR-513a-5p significantly affected NEDD4L-inhibited WNT signaling and reduced TMZ cytotoxicity. 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Furthermore, a", "ts with normal controls using microarray and RNA sequencing (RNA Seq) data from TCGA database, we found", "ormal control groups from the microarray and RNA sequencing (RNA Seq) data of TCGA database. Detection o"], "order_basis": "paper_text_order:1329", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ls and methods Cell culture, treatments, and transfection Minimum essential Eagle medium (MEM) was use", "tured cells for another 48 h. To conduct the transfection experiments, cells were seeded into a 12-wel", "LO 3’UTR reporter plasmids were respectively transfected with Lipofectamine 3000 (Invitrogen) accordi", "uced glioma cell viability. After cells were transfected with the indicated doses of NEDD4L cDNA-cont"], "order_basis": "paper_text_order:1991", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ses of IGF-1 and TMZ were added to overnight-cultured cells for the indicated times. For inhibitor", "then 200 ng/ml IGF-1 was added to overnight-cultured cells for another 48 h. To conduct the trans"], "order_basis": "paper_text_order:2654", "id": "assay:3"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["L in GBM patients with normal controls using microarray and RNA sequencing (RNA Seq) data from TCGA", "s compared to normal control groups from the microarray and RNA sequencing (RNA Seq) data of TCGA da"], "order_basis": "paper_text_order:3978", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["mRNA levels were respectively measured by an immunoblotting assay and a real-time PCR. β-Actin and GAPDH", "24 h, NEDD4L protein levels were measured by immunoblotting assays. Cell viability was measured by an MT"], "order_basis": "paper_text_order:5186", "id": "assay:5"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ly measured by an immunoblotting assay and a real-time PCR. β-Actin and GAPDH levels were used as inter"], "order_basis": "paper_text_order:5213", "id": "assay:6"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ng assays. Cell viability was measured by an MTT assay. Data are the mean ± SD of three indep"], "order_basis": "paper_text_order:5670", "id": "assay:7"}]}