MicroRNA‑153‑3p suppresses retinoblastoma cell growth and invasion via targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34036380", "kind": "science-record", "revision": 7, "content_hash": "sha256:bcd29cfa743ed87e4a5302d1bc7555b06466c68decad98d9aa82b1270f73223f", "created_at": "2026-11-01T15:41:36Z", "updated_at": "2026-11-01T22:03:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MicroRNA‑153‑3p suppresses retinoblastoma cell growth and invasion via targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways.", "doi": "10.3892/ijo.2021.5227", "pmid": "34036380", "authors": ["Long Guo", "Yu Bai", "Tianyu Ni", "Yuan Li", "Rong Cao", "Shuzhe Ji", "Shuzhen Li"], "journal": "International journal of oncology", "year": 2021, "abstract": "Mounting evidence has demonstrated that microRNAs (miRNAs or miRs) play significant roles in various types of human tumors, including retinoblastoma (RB). However, the biological role and regulatory mechanisms of miRNAs in RB remain to be fully elucidated. The present study was designed to identify the regulatory effects of miRNAs in RB and the underlying mechanisms. Differentially expressed miRNAs in RB tissue were screened out based on the Gene Expression Omnibus (GEO) dataset, GSE7072, which revealed that miR‑153 in particular, displayed the highest fold change in expression. It was identified that miR‑153 was significantly downregulated in RB tissues, and its downregulation was closely associated with a larger tumor base and differentiation. Functional analysis revealed that the overexpression of miR‑153 inhibited RB cell proliferation, migration and invasion, and promoted the apoptosis of WERI‑RB‑1 and Y79 cells. In addition, insulin‑like growth factor 1 receptor (IGF1R) was identified as a target of miR‑153 in RB cells. More importantly, it was demonstrated that miR‑153 upregulation inhibited the expression of its target gene, IGF1R, which inhibited the activation of the Raf/MEK and PI3K/AKT signaling pathways. Collectively, the present study demonstrates for the first time, to the best of our knowledge, that miR‑153 functions as a tumor suppressor in RB by targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways. Collectively, the findings presented herein demonstrate that miR‑153 targets IGF1R and blocks the activation of the Raf/MEK and PI3K/AKT signaling pathway, thus preventing the progression of RB. Thus, this miRNA may serve as a novel prognostic biomarker and therapeutic target for RB.", "claims": [{"id": "claim-method", "statement": "Differentially expressed miRNAs (DEmiRNAs) between normal and RB samples were screened based on GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34036380", "locator": "sections[7] \"Microarray datasets\" paragraph 2", "quote": "Differentially expressed miRNAs (DEmiRNAs) between normal and RB samples were screened based on GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool."}], "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:34036380", "locator": "sections[28] \"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"}], "gaps": []}, "experiment": {"state": "partial", "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:34036380"], "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:GSE7072"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE7072"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34036380", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/ijo.2021.5227", "sha256": "sha256:1a9b1f4a3753caef6445f758ddc6024b939490cffb515d11e63b886296ed90ca", "bytes": 55431, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3892/ijo.2021.5227", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8143749", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE7072", "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=GSE7072", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE7072", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM169532", "GSM169533", "GSM169534", "GSM169535", "GSM170842", "GSM170986"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "4879", "taxon": "Homo sapiens", "title": "Profiling miRNAs in human retinoblastoma", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34036380:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fbeb88d7304f2e9869997570e216293b86258c82a16ee767f6ac3d2f4f01120a", "bytes": 594, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#tI-ijo-59-01-05227", "version": null, "note": "Sequences of the primers used in the present study.", "structure": {"pmcid": "PMC8143749", "section_index": 4, "section_title": "RT-qPCR", "row_count": 9, "column_count": 2}, "table": {"label": "Table I", "caption": "Sequences of the primers used in the present study.", "rows": [["Gene", "Primer sequence"], ["miR-153-3p", "F: 5′-ACACTCCAGCTGGGTTGCATAGTCACAAA-3′"], ["R: 5′-CAGTGCGTGTCGTGGAGT-3′"], ["U6", "F: 5′-TCGCACAGACTTGTGGGAGAA-3′"], ["R: 5′-CGCACATTAAGCCTCTATAGTTACTAGG-3′"], ["IGF1R", "F: 5′-GGGGCTCCTGTTTCTCTCC-3′"], ["R: 5′-GCCTTGGAGATGAGCAGGAT-3′"], ["GAPDH", "F: 5′-AGCTTGTCATCAACGGGAAG-3′"], ["R: 5′-TTTGATGTTAGTGGGGTCTCG-3′"]], "row_count": 9, "column_count": 2, "numeric_cells": 9, "header_rows": 1, "locator": "section[4]/table-wrap[1]#tI-ijo-59-01-05227"}}, {"id": "asset:table:pmid:34036380:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5d01a2131e4959b9d8564a53708d7ecb2cc9568b4e299108844b0b3d4d024860", "bytes": 1012, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tII-ijo-59-01-05227", "version": null, "note": "Association between miR-153-3p and clinicopathological features of patients with retinoblastoma.", "structure": {"pmcid": "PMC8143749", "section_index": 18, "section_title": "miR-153 expression is downregulated in RB tissues and cell lines", "row_count": 23, "column_count": 5}, "table": {"label": "Table II", "caption": "Association between miR-153-3p and clinicopathological features of patients with retinoblastoma.", "rows": [["Feature", "Total n=50", "miR-153-3p expression", "P-value"], ["High", "Low"], ["Sex", "", "", "", "0.4741"], ["Male", "21", "8", "13", ""], ["Female", "29", "14", "15", ""], ["Age at presentation (years)", "", "", "", "0.1212"], ["≤5", "31", "11", "20", ""], [">5", "19", "11", "8", ""], ["Tumor enucleation location", "", "", "", "0.1443"], ["Right", "24", "8", "16", ""], ["Left", "26", "14", "12", ""], ["Largest tumor base (mm)", "", "", "", "0.0199a"], ["≤15", "32", "18", "14", ""], [">15", "18", "4", "14", ""], ["T classification", "", "", "", "0.1830"], ["T1-2", "28", "10", "18", ""], ["T3-4", "22", "12", "10", ""], ["Clinical stage", "", "", "", "0.2008"], ["I-II", "20", "11", "9", ""], ["III-IV", "30", "11", "19", ""], ["Differentiation", "", "", "", "0.0025b"], ["Well and moderate", "16", "12", "4", ""], ["Poor", "34", "10", "24", ""]], "row_count": 23, "column_count": 5, "numeric_cells": 57, "header_rows": 2, "locator": "section[18]/table-wrap[1]#tII-ijo-59-01-05227"}}], "gaps": ["asset:data:geo:GSE7072 not downloaded", "asset:data:geo:GSE7072 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"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": "ANOVA"}}, {"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": "Kaplan-Meier"}}, {"id": "method-4", "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": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-5", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson's correlation"}}, {"id": "method-6", "family": null, "specific": null, "label": "GEO2R", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed miRNAs (DEmiRNAs) between normal and RB samples were screened based on GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_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": ["GSE7072"], "resolved_accessions": ["GSE7072"], "statements": ["The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE7072 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": [], "assets": ["source:pmid:34036380", "data:geo:GSE7072", "asset:table:pmid:34036380:1", "asset:table:pmid:34036380:2"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE7072"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 46494, "completion_tokens": 928, "cached_tokens": 784}}, "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:34036380", "type": "paper", "label": "pmid:34036380"}, {"id": "source:pmid:34036380", "type": "manuscript", "label": "PMID 34036380 full text"}, {"id": "data:geo:GSE7072", "type": "dataset", "label": "GEO GSE7072"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34036380", "type": "paper", "label": "pmid:34036380"}, {"id": "source:pmid:34036380", "type": "manuscript", "label": "PMID 34036380 full text"}, {"id": "data:geo:GSE7072", "type": "dataset", "label": "GEO GSE7072"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34036380", "type": "extraction", "used": ["source:pmid:34036380"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE7072", "type": "accession_resolution", "used": ["data:geo:GSE7072"], "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:34036380", "parent_hash": "sha256:be4e0d5d5a401c4bc5212b3cac4f7a45202098143fabcc00945c0dc5e4374893", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE7072 licence not read", "asset:data:geo:GSE7072 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "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": 0.69, "evidence": ["on, migration and invasion, and promoted the apoptosis of WERI‑RB‑1 and Y79 cells. In addition, ins"], "order_basis": "paper_text_order:987", "id": "assay:1"}, {"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": ["rsity (Zhongshan, China). All the cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Hy"], "order_basis": "paper_text_order:2976", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student's t-test"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}