Downregulation of miR‑486‑5p in papillary thyroid carcinoma tissue: A study based on microarray and miRNA sequencing.

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In the present study, the aim was to explore miR‑486‑5p expression and its role in PTC, as well as to investigate the biological function of its potential target genes. The expression levels of miR‑486‑5p and its clinicopathological significance were examined in 507 PTC and 59 normal thyroid samples via The Cancer Genome Atlas (TCGA). Subsequently, the results were validated using data from Gene Expression Omnibus (GEO) and ArrayExpress. Receiver operating characteristic and summary receiver operating characteristic curves were used to assess the ability of miR‑486‑5p in distinguishing PTC from normal tissue. Furthermore, potential miR‑486‑5p mRNA targets were identified using 12 prediction tools and enrichment analysis was performed on the encoding genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The expression levels of miR‑486‑5p were consistently downregulated in PTC compared with in normal tissue across datasets from TCGA, GEO (GSE40807, GSE62054 and GSE73182) and ArrayExpress (E‑MTAB‑736). The results also demonstrated that miR‑486‑5p expression was associated with cancer stage (P=0.003), pathologic lymph node (P=0.047), metastasis (P=0.042), neoplasm (P=0.012) and recurrence (P=0.016) in patients with PTC. In addition, low expression of miR‑486‑5p in patients with PTC was associated with a worse overall survival. A total of 80 miR‑486‑5p‑related genes were observed from at least 9 of 12 prediction platforms, and these were involved in 'hsa05200: Pathways in cancer' and 'hsa05206: MicroRNAs in cancer'. Finally, three hub genes, CRK like proto‑oncogene, phosphatase and tensin homolog and tropomyosin 3, were identified as important candidates in tumorigenesis and progression of PTC. In conclusion, it may be hypothesized that miR‑486‑5p contributes towards PTC onset and progression, and may act as a clinical target. However, in vitro and in vivo experiments are required to validate the findings of the present study.", "claims": [{"id": "claim-method", "statement": "The pooled SMD of miR-486-5p was −1.358 [95% CI, −1.950-(−0.766); P<0.001; Fig. 5A] by the random effects model, and the P-value of the heterogeneity test was 0.001 (I2=75.6%).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30015845", "locator": "sections[13] \"Further verification of miR-486-5p downregulation in PTC using SMD and SROC\" paragraph 2", "quote": "The pooled SMD of miR-486-5p was −1.358 [95% CI, −1.950-(−0.766); P<0.001; Fig. 5A] by the random effects model, and the P-value of the heterogeneity test was 0.001 (I2=75.6%)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30015845", "locator": "sections[20] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A random-effects meta-analysis of miR-486-5p expression data from TCGA, GEO and ArrayExpress, including 603 PTC and 125 normal thyroid tissue samples, yielded a pooled SMD of −1.358 (95% CI, −1.950–(−0.766); P<0.001), confirming miR-486-5p downregulation in PTC.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "The pooled SMD of miR-486-5p was −1.358 [95% CI, −1.950-(−0.766); P<0.001; Fig. 5A] by the random effects model, and the P-value of the heterogeneity test was 0.001 (I2=75.6%)."}, "evidence": [{"asset": "source:pmid:30015845", "locator": "sections[13] \"Further verification of miR-486-5p downregulation in PTC using SMD and SROC\" paragraph 2", "quote": "miR-486-5p expression data from TCGA, GEO (GSE40807, GSE57780, GSE62054 and GSE73182) and ArrayExpress (E-MTAB-736) were combined for meta-analysis, which included a total of 603 PTC and 125 normal tissue samples (Table II)."}, {"asset": "source:pmid:30015845", "locator": "sections[13] \"Further verification of miR-486-5p downregulation in PTC using SMD and SROC\" paragraph 2", "quote": "The pooled SMD of miR-486-5p was −1.358 [95% CI, −1.950-(−0.766); P<0.001; Fig. 5A] by the random effects model, and the P-value of the heterogeneity test was 0.001 (I2=75.6%)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A random-effects meta-analysis of miR-486-5p expression data from TCGA, GEO and ArrayExpress, including 603 PTC and 125 normal thyroid tissue samples, yielded a pooled SMD of −1.358 (95% CI, −1.950–(−0.766); P<0.001), confirming miR-486-5p downregulation in PTC.", "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:30015845"], "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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