{"doi":"10.1111/jcmm.13968","title":"MiR‐30‐5p suppresses cell chemoresistance and stemness in colorectal cancer through <scp>USP</scp>22/Wnt/β‐catenin signaling axis","abstract":"<jats:title>Abstract</jats:title><jats:p>Colorectal cancer (<jats:styled-content style=\"fixed-case\">CRC</jats:styled-content>) remains both common and fatal, and its successful treatment is greatly limited by the development of stem cell‐like characteristics (stemness) and chemoresistance. MiR‐30‐5p has been shown to function as a tumor suppressor by targeting the Wnt/β‐catenin signaling pathway, but its activity in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> has never been assessed. We hypothesized that miR‐30‐5p exerts anti‐oncogenic effects in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> by regulating the <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22/Wnt/β‐catenin signaling axis. In the present study, we demonstrate that tissues from <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> patients and human <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cell lines show significantly decreased miR‐30‐5p family expression. After identifying the 3’<jats:styled-content style=\"fixed-case\">UTR</jats:styled-content> of <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 as a potential binding site of miR‐30‐5p, we constructed a luciferase reporter containing the potential miR‐30‐5p binding site and measured the effects on <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 expression. Western blot assays showed that miR‐30‐5p decreased <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 protein expression in <jats:styled-content style=\"fixed-case\">HEK</jats:styled-content>293 and Caco2 <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells. To evaluate the effects of miR‐30‐5p on <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cell stemness, we isolated <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 + <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells (Caco2 and <jats:styled-content style=\"fixed-case\">HCT</jats:styled-content>15). We then determined that, while miR‐30‐5p is normally decreased in <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 + <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells, miR‐30‐5p overexpression significantly reduces expression of stem cell markers <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 and Sox2, sphere formation, and cell proliferation. Similarly, we found that miR‐30‐5p expression is normally reduced in 5‐fluorouracil (5‐<jats:styled-content style=\"fixed-case\">FU</jats:styled-content>) resistant <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells, whereas miR‐30‐5p overexpression in 5‐<jats:styled-content style=\"fixed-case\">FU</jats:styled-content> resistant cells reduces sphere formation and cell viability. Inhibition of miR‐30‐5p reversed the process. Finally, we determined that miR‐30‐5p attenuates the expression of Wnt/β‐catenin signaling target genes (Axin2 and <jats:styled-content style=\"fixed-case\">MYC</jats:styled-content>), Wnt luciferase activity, and β‐catenin protein levels in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> stem cells.</jats:p>","journal":"Journal of Cellular and Molecular Medicine","year":2019,"id":649837,"datarank":0.6496100010429497,"base_score":4.330733340286331,"endowment":4.330733340286331,"self_citation_contribution":0.6496100010429497,"citation_network_contribution":0.0,"self_endowment_contribution":0.6496100010429497,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":75,"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":1694197,"name":"Dazhuang Miao","orcid":null,"position":1,"is_corresponding":false},{"id":1694198,"name":"Muhong Wang","orcid":null,"position":2,"is_corresponding":false},{"id":1694199,"name":"Jiachen Lv","orcid":null,"position":3,"is_corresponding":false},{"id":473076,"name":"Yihui Wang","orcid":"0000-0002-7718-3816","position":4,"is_corresponding":false},{"id":1694200,"name":"Jinxue Tong","orcid":"0000-0001-8896-0898","position":5,"is_corresponding":false},{"id":1694195,"name":"Shixiong Jiang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MiR‐30‐5p suppresses cell chemoresistance and stemness in colorectal cancer through <scp>USP</scp>22/Wnt/β‐catenin signaling axis","abstract":"<jats:title>Abstract</jats:title><jats:p>Colorectal cancer (<jats:styled-content style=\"fixed-case\">CRC</jats:styled-content>) remains both common and fatal, and its successful treatment is greatly limited by the development of stem cell‐like characteristics (stemness) and chemoresistance. MiR‐30‐5p has been shown to function as a tumor suppressor by targeting the Wnt/β‐catenin signaling pathway, but its activity in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> has never been assessed. We hypothesized that miR‐30‐5p exerts anti‐oncogenic effects in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> by regulating the <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22/Wnt/β‐catenin signaling axis. In the present study, we demonstrate that tissues from <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> patients and human <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cell lines show significantly decreased miR‐30‐5p family expression. After identifying the 3’<jats:styled-content style=\"fixed-case\">UTR</jats:styled-content> of <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 as a potential binding site of miR‐30‐5p, we constructed a luciferase reporter containing the potential miR‐30‐5p binding site and measured the effects on <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 expression. Western blot assays showed that miR‐30‐5p decreased <jats:styled-content style=\"fixed-case\">USP</jats:styled-content>22 protein expression in <jats:styled-content style=\"fixed-case\">HEK</jats:styled-content>293 and Caco2 <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells. To evaluate the effects of miR‐30‐5p on <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cell stemness, we isolated <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 + <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells (Caco2 and <jats:styled-content style=\"fixed-case\">HCT</jats:styled-content>15). We then determined that, while miR‐30‐5p is normally decreased in <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 + <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells, miR‐30‐5p overexpression significantly reduces expression of stem cell markers <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>133 and Sox2, sphere formation, and cell proliferation. Similarly, we found that miR‐30‐5p expression is normally reduced in 5‐fluorouracil (5‐<jats:styled-content style=\"fixed-case\">FU</jats:styled-content>) resistant <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> cells, whereas miR‐30‐5p overexpression in 5‐<jats:styled-content style=\"fixed-case\">FU</jats:styled-content> resistant cells reduces sphere formation and cell viability. Inhibition of miR‐30‐5p reversed the process. Finally, we determined that miR‐30‐5p attenuates the expression of Wnt/β‐catenin signaling target genes (Axin2 and <jats:styled-content style=\"fixed-case\">MYC</jats:styled-content>), Wnt luciferase activity, and β‐catenin protein levels in <jats:styled-content style=\"fixed-case\">CRC</jats:styled-content> stem cells.</jats:p>","is_dataset_classified":null,"base_score":4.330733340286331,"endowment":4.330733340286331,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30338942","pmcid":"PMC6307779","openalex_id":"https://openalex.org/W2896888626","authors":[],"funders":[],"total_grants":0,"fwci":2.6666,"citation_percentile":0.91409508,"influential_citations":0,"citation_trend":[{"year":2019,"count":8},{"year":2020,"count":9},{"year":2021,"count":22},{"year":2022,"count":16},{"year":2023,"count":8},{"year":2024,"count":5},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.13968","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.13968","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjcmm.13968","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13968","host_type":"publisher"},{"url":"https://doi.org/10.1111/jcmm.13968","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30338942","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC6307779","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6307779","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6307779","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6307779?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["MicroRNA in disease regulation","Circular RNAs in diseases","Wnt/β-catenin signaling in development and cancer"],"mesh_terms":["Cell Line","Fluorouracil","Humans","Neoplastic Stem Cells","Colorectal Neoplasms","Gene Expression Regulation, Neoplastic","Caco-2 Cells","Drug Resistance, Neoplasm","HT29 Cells","MicroRNAs","Ubiquitin Thiolesterase","HCT116 Cells","Cell Line, Tumor","Cell Proliferation","beta Catenin","SOXB1 Transcription Factors","HEK293 Cells","Wnt Signaling Pathway"],"keywords":["Wnt signaling pathway","SOX2","Cancer research","Colorectal cancer","Cell growth","Catenin","Viability assay","microRNA","LGR5","Stem cell","HEK 293 cells","Signal transduction","Cancer stem cell","Biology","Cell culture","Western blot","KLF4","Chemistry","Cancer","Cell biology","Embryonic stem cell","Genetics","Gene","Chemoresistance","Stemness","Usp22","Wnt/β-catenin Signaling","Mir-30-5p"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T04:24:24.505929Z","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":[]}