{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:09:58Z","timestamp":1780304998038,"version":"3.54.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acquired resistance to 5\u2010fluorouracil (5\u2010FU) is a primary clinical challenge in colorectal cancer (CRC) treatment. Our study aimed to identify key factors predictive of 5\u2010FU resistance and to elucidate their functional mechanisms by combining multi\u2010omics analysis with experimental verification. The prognostic model was constructed based on the gene expression omnibus (GEO, GSE196900, GSE166555) and the cancer genome atlas (TCGA)\u2010Colon Adenocarcinoma (COAD) datasets combined with regression analysis. Kaplan\u2013Meier (K\u2010M), receiver operating characteristic (ROC) curve, and nomogram were used to evaluate the predictive performance of the prognostic model. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used for functional enrichment analysis. Single\u2010cell RNA sequencing (scRNA\u2010seq, GSE166555) and qRT\u2010PCR analysis were used to analyze the tumor microenvironment and gene expression. In cell experiments, CCK\u20108 assay measured IC\n                    <jats:sub>50<\/jats:sub>\n                    value. Glycolysis metabolism was evaluated by detecting glucose consumption, lactic acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR); cell stemness was evaluated by sphere formation assay. A 5\u2010gene prognostic model was successfully constructed, which could effectively distinguish the high\u2212\/low\u2010risk groups of CRC patients and was significantly correlated with overall survival. Ribosome binding protein 1 (RRBP1) is highly expressed in cancer tissues of non\u2010responders to chemotherapy. It is also highly expressed in tumor epithelial cells, and its high expression is closely related to aneuploidy characteristics, up\u2010regulation of oncogenes, and activation of pro\u2010survival pathways. In\u00a0vitro experiments confirmed that knockdown of RRBP1 significantly enhanced the sensitivity of CRC cells to 5\u2010FU and inhibited cell proliferation. Mechanistically, RRBP1 knockdown effectively reversed the enhanced glycolysis activity and stem cell\u2010like properties of 5\u2010FU\u2010resistant cells. This study established RRBP1 as a key CRC prognostic factor and 5\u2010FU resistance driver, operating through the regulation of cell glycolysis and stemness. RRBP1 emerges as a new biomarker and therapeutic target for predicting the efficacy of 5\u2010FU.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70265","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:54:36Z","timestamp":1772967276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of 5\u2010Gene Prognostic Markers and Functional Verification of\n                    <scp>RRBP1<\/scp>\n                    in 5\u2010Fluorouracil Resistance of Colorectal Cancer by Multi\u2010Omics Analysis and Experimental Verification"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5242-2334","authenticated-orcid":false,"given":"Hui","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Henan Provincial People's Hospital, People's Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Henan Provincial People's Hospital, People's Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Henan Provincial People's Hospital, People's Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongmei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Henan Provincial People's Hospital, People's Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-020-0375-y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.0106"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.315"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216420"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.855674"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-13086-9"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70105"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.103920"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020664"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3119375"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01634-6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1529029"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06451-w"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-84353-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11714"},{"key":"e_1_2_12_17_1","article-title":"The Role of Endoplasmic Reticulum Stress in Promoting Aerobic Glycolysis in Cancer Cells: An Overview","volume":"251","author":"Jalil A. 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