{"doi":"10.1002/ijc.25506","title":"Micro‐RNA‐21 regulates TGF‐β‐induced myofibroblast differentiation by targeting PDCD4 in tumor‐stroma interaction","abstract":"<jats:title>Abstract</jats:title><jats:p>Transforming growth factor‐β1 (TGF‐β1) induces stromal fibroblast‐to‐myofibroblast transdifferentiation in the tumor‐stroma interactive microenvironment <jats:italic>via</jats:italic> modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro‐RNAs (miRNAs) and their roles in TGF‐β1‐induced myofibroblast differentiation in tumor‐stroma interaction are unclear. Using quantitative real‐time RT‐PCR, we demonstrated that the expression of micro‐RNA‐21 (miR‐21) was upregulated in activated fibroblasts after treatment with TGF‐β1 or conditioned medium from cancer cells. To determine the potential roles of miR‐21 in TGF‐β1‐mediated gene regulation during myofibroblast conversion, we showed that miR‐21 expression was downregulated by miR‐21 inhibitor and upregulated by miR‐21 mimic. Interestingly, downregulation of miR‐21 with the inhibitor effectively inhibited TGF‐β1‐induced myofibroblast differentiation while upregulation of miR‐21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR‐21 directly targeted and downregulated programmed cell death 4 (<jats:italic>PDCD4</jats:italic>) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR‐21 participated in TGF‐β1‐induced myofibroblast transdifferentiation in cancer stroma by targeting <jats:italic>PDCD4</jats:italic>.</jats:p>","journal":"International Journal of Cancer","year":2011,"id":659563,"datarank":0.7181237614173069,"base_score":4.787491742782046,"endowment":4.787491742782046,"self_citation_contribution":0.7181237614173069,"citation_network_contribution":0.0,"self_endowment_contribution":0.7181237614173069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":119,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1721758,"name":"Siyu Cao","orcid":null,"position":1,"is_corresponding":false},{"id":383445,"name":"Chun Li","orcid":"0000-0002-2376-4703","position":2,"is_corresponding":false},{"id":1721759,"name":"Asferd Mengesha","orcid":null,"position":3,"is_corresponding":false},{"id":542556,"name":"Beihua Kong","orcid":"0000-0002-5911-0242","position":4,"is_corresponding":false},{"id":1721760,"name":"Mingqian Wei","orcid":null,"position":5,"is_corresponding":false},{"id":640362,"name":"Qin Yao","orcid":"0000-0003-4485-4545","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Micro‐RNA‐21 regulates TGF‐β‐induced myofibroblast differentiation by targeting PDCD4 in tumor‐stroma interaction","abstract":"<jats:title>Abstract</jats:title><jats:p>Transforming growth factor‐β1 (TGF‐β1) induces stromal fibroblast‐to‐myofibroblast transdifferentiation in the tumor‐stroma interactive microenvironment <jats:italic>via</jats:italic> modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro‐RNAs (miRNAs) and their roles in TGF‐β1‐induced myofibroblast differentiation in tumor‐stroma interaction are unclear. Using quantitative real‐time RT‐PCR, we demonstrated that the expression of micro‐RNA‐21 (miR‐21) was upregulated in activated fibroblasts after treatment with TGF‐β1 or conditioned medium from cancer cells. To determine the potential roles of miR‐21 in TGF‐β1‐mediated gene regulation during myofibroblast conversion, we showed that miR‐21 expression was downregulated by miR‐21 inhibitor and upregulated by miR‐21 mimic. Interestingly, downregulation of miR‐21 with the inhibitor effectively inhibited TGF‐β1‐induced myofibroblast differentiation while upregulation of miR‐21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR‐21 directly targeted and downregulated programmed cell death 4 (<jats:italic>PDCD4</jats:italic>) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR‐21 participated in TGF‐β1‐induced myofibroblast transdifferentiation in cancer stroma by targeting <jats:italic>PDCD4</jats:italic>.</jats:p>","is_dataset_classified":null,"base_score":4.787491742782046,"endowment":4.787491742782046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20533548","pmcid":null,"openalex_id":"https://openalex.org/W2090786835","authors":[],"funders":[],"total_grants":0,"fwci":3.1833,"citation_percentile":0.91773257,"influential_citations":0,"citation_trend":[{"year":2012,"count":13},{"year":2013,"count":9},{"year":2014,"count":11},{"year":2015,"count":14},{"year":2016,"count":10},{"year":2017,"count":9},{"year":2018,"count":10},{"year":2019,"count":5},{"year":2020,"count":6},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.25506","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.25506","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.25506","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.25506","host_type":"publisher"},{"url":"https://doi.org/10.1002/ijc.25506","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20533548","host_type":"repository"},{"url":"http://hdl.handle.net/10072/41450","host_type":"repository"}],"fields_of_study":["Cancer-related molecular mechanisms research","MicroRNA in disease regulation","Circular RNAs in diseases","Apoptosis Regulatory Proteins","Blotting, Western","Cell Differentiation","Cells, Cultured","Colonic Neoplasms","Culture Media, Conditioned","Female","Fetus","Fibroblasts","Fluorescent Antibody Technique","Gene Expression Regulation","Humans","Lung","MicroRNAs","Myofibroblasts","Ovarian Neoplasms","RNA, Messenger","RNA-Binding Proteins","Reverse Transcriptase Polymerase Chain Reaction","Stromal Cells","Transforming Growth Factor beta","Tumor Microenvironment"],"mesh_terms":["Cell Differentiation","Cells, Cultured","Colonic Neoplasms","Female","Fetus","Fibroblasts","Fluorescent Antibody Technique","Gene Expression Regulation","Humans","Lung","Ovarian Neoplasms","RNA, Messenger","Blotting, Western","Transforming Growth Factor beta","RNA-Binding Proteins","Culture Media, Conditioned","Stromal Cells","Reverse Transcriptase Polymerase Chain Reaction","MicroRNAs","Apoptosis Regulatory Proteins","Myofibroblasts","Tumor Microenvironment"],"keywords":["Myofibroblast","Transdifferentiation","Downregulation and upregulation","Transforming growth factor","Stroma","Cell biology","microRNA","Cancer research","Stromal cell","Biology","Fibroblast","Pathology","Cell culture","Immunology","Fibrosis","Gene","Stem cell","Medicine","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T07:10:22.329444Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}