OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial-Mesenchymal Transition: Evidence from Bioinformatics Data Mining and Experimental Verification.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35418782", "kind": "science-record", "revision": 4, "content_hash": "sha256:3427fe42d8acb6773cffddd9fb6a30496dfa82f731be9280f83a59d076ceddbf", "created_at": "2026-11-01T18:14:14Z", "updated_at": "2026-11-01T22:06:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial-Mesenchymal Transition: Evidence from Bioinformatics Data Mining and Experimental Verification.", "doi": "10.2147/CMAR.S345299", "pmid": "35418782", "authors": ["Shuai Guo", "Yang Sun"], "journal": "Cancer management and research", "year": 2022, "abstract": "Introduction: Colorectal cancer (CRC) represents one of the most frequent human malignancies with its underlying pathogenesis still unclear. The prevalence of multi-omics in screening biomarkers associated with CRC has largely accelerated our understanding into the pathophysiology of CRC. The present work aimed to mine the Gene Expression Omnibus (GEO) datasets associated with CRC studies and identify potential targets correlated with CRC pathogenesis.\nMethods: We screened the DEGs in GSE50760 and GSE104178 and performed functional Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, the overlapped DEGs were subjected to functional GO enrichment and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network and miRNA-mRNA network were constructed based on the overlapped DEGs. The in vitro functional assays including qRT-PCR, caspase-3 and -9 activity assay, wound healing assay, CCK-8 assay and luciferase reporter assay were performed to determine the role of OTOP2/miR-3148 axis in regulating CRC cell progression.\nResults: Fifty-three overlapped genes were screened over GSE50760 and GSE104178 and ten hub genes were identified by PPI network analysis. Expression levels of GCG, SST, NPY, GUCA2B, PYY, UCN3, GUCA2A, TMEM82 and BEST4 were not correlated with the overall survival of patients with CRC. However, the high expression of otopetrin 2 (OTOP2) in the CRC tissues was significantly correlated with better overall survival of patients with CRC. The expression of OTOP2 in CRC tissues was significantly lowever than that in normal ones. The in vitro functional assays demonstrated that OTOP2 silence reduced caspase-3/-9 activities, promoted cell migration, proliferation and epithelial-mesenchymal transition in HT29 and SW620 cells. Furthermore, miR-3148 could inversely regulate OTOP2 expression in CRC cell lines.\nConclusion: Collectively, the work suggested the potential role of the OTOP2/miR-3148 axis in the pathophysiology of CRC by mining the GEO database.", "claims": [{"id": "claim-method", "statement": "Survival analysis of hub genes was assessed with Kaplan Meier plotter,25 which is capable of assessing the effect of 54 k genes (mRNA, miRNA, protein) on survival in 21 cancer types.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35418782", "locator": "sections[7] \"Survival Analysis\" paragraph 2", "quote": "Survival analysis of hub genes was assessed with Kaplan Meier plotter,25 which is capable of assessing the effect of 54 k genes (mRNA, miRNA, protein) on survival in 21 cancer types."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data are available upon request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35418782", "locator": "sections[27] \"Data Sharing Statement\" paragraph 2", "quote": "All the data are available upon request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Fifty-three overlapped genes were screened over GSE50760 and GSE104178 and ten hub genes were identified by PPI network analysis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35418782", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Fifty-three overlapped genes were screened over GSE50760 and GSE104178 and ten hub genes were identified by PPI network analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Fifty-three overlapped genes were screened over GSE50760 and GSE104178 and ten hub genes were identified by PPI network analysis.", "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:35418782"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104178"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104178"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35418782", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/CMAR.S345299", "sha256": "sha256:6f8ff18b5c67ce4c0f2a3ef30f0a7f466857aa05d4275d7cbdae4922e5be3d2a", "bytes": 41177, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/CMAR.S345299", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9000554", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE104178", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104178", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE104178", "version": null, "note": "All the data are available upon request from the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the data are available upon request from the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2791405", "GSM2791406", "GSM2791407", "GSM2791408", "GSM2791409", "GSM2791410"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "RNA-Sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE50760", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50760", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50760", "version": null, "note": "All the data are available upon request from the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the data are available upon request from the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1228184", "GSM1228185", "GSM1228186", "GSM1228187", "GSM1228188", "GSM1228189", "GSM1228190", "GSM1228191", "GSM1228192", "GSM1228193", "GSM1228194", "GSM1228195", "GSM1228196", "GSM1228197", "GSM1228198", "GSM1228199", "GSM1228200", "GSM1228201", "GSM1228202", "GSM1228203", "GSM1228204", "GSM1228205", "GSM1228206", "GSM1228207", "GSM1228208", "GSM1228209", "GSM1228210", "GSM1228211", "GSM1228212", "GSM1228213", "GSM1228214", "GSM1228215", "GSM1228216", "GSM1228217", "GSM1228218", "GSM1228219", "GSM1228220", "GSM1228221", "GSM1228222", "GSM1228223", "GSM1228224", "GSM1228225", "GSM1228226", "GSM1228227", "GSM1228228", "GSM1228229", "GSM1228230", "GSM1228231", "GSM1228232", "GSM1228233", "GSM1228234", "GSM1228235", "GSM1228236", "GSM1228237"], "sample_count": 54, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Gene expression profiling study by RNA-seq in colorectal cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE104178 not downloaded", "asset:data:geo:GSE104178 licence not read", "asset:data:geo:GSE50760 not downloaded", "asset:data:geo:GSE50760 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Survival analysis of hub genes was assessed with Kaplan Meier plotter,25 which is capable of assessing the effect of 54 k genes (mRNA, miRNA, protein) on survival in 21 cancer types."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "KM"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE50760", "GSE104178"], "resolved_accessions": ["GSE50760", "GSE104178"], "statements": ["All the data are available upon request from the corresponding author."], "basis": "The paper names GSE50760, GSE104178 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:35418782", "data:geo:GSE104178"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE104178"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:41:43Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12470, "completion_tokens": 1589, "cached_tokens": 188}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35418782", "type": "paper", "label": "pmid:35418782"}, {"id": "source:pmid:35418782", "type": "manuscript", "label": "PMID 35418782 full text"}, {"id": "data:geo:GSE104178", "type": "dataset", "label": "GEO GSE104178"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35418782", "type": "paper", "label": "pmid:35418782"}, {"id": "source:pmid:35418782", "type": "manuscript", "label": "PMID 35418782 full text"}, {"id": "data:geo:GSE104178", "type": "dataset", "label": "GEO GSE104178"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35418782", "type": "extraction", "used": ["source:pmid:35418782"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE104178", "type": "accession_resolution", "used": ["data:geo:GSE104178"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35418782", "parent_hash": "sha256:397f919c913024e51ed1455d5232d13fbef0f94002ed02fc21eb24ddbf94dc2b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE104178 licence not read", "asset:data:geo:GSE104178 not downloaded", "asset:data:geo:GSE50760 licence not read", "asset:data:geo:GSE50760 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and -9 activity assay, wound healing assay, CCK-8 assay and luciferase reporter assay were per", "n vitro functional assays including qRT-PCR, caspase-3 and -9 activity assay, wound healing assay", "says demonstrated that OTOP2 silence reduced caspase-3/-9 activities, promoted cell migration, pr"], "order_basis": "paper_text_order:1077", "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": ["s defined as *P<0.05. Cell Culture and siRNA Transfection The CRC cell lines including HT29 and SW620", "iRNAs (si-NC, si-OTOP2#1 or si-OTOP2#2) were transfected into the HT29 or SW620 cells by using Lipofe", "nce was defined as *P<0.05. Cell Culture and siRNA Transfection The CRC cell lines including HT", "(Guangzhou, China). The respective scrambled siRNA (named si-NC) was used as the negative contr"], "order_basis": "paper_text_order:2825", "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": 0.77, "evidence": ["anassas, USA). The HT29 and SW620 cells were cultured in DMEM medium supplemented with 10% fetal bovi"], "order_basis": "paper_text_order:2978", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["the protein expression of OTOP2 evaluated by IHC was significantly lower in the CRC tissues t"], "order_basis": "paper_text_order:5186", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Survival analysis of hub genes was assessed with Kaplan Meier plotter,25 which is capable of assessing the effect of 54 k genes (mRNA, miRNA, protein) on survival in 21 cancer types."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}