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Mechanistically, NMB protein stability depended on USP21-mediated deubiquitination, activating the NF-kB/P65 cascade. NMB expression also correlated with 5-fluorouracil resistance, supporting relevance to chemotherapy 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did the study propose for how NMB promotes tumor progression?",{"text":72,"@type":64},"NMB protein stability is regulated by USP21-dependent deubiquitination, which activates the NF-kB signaling cascade and drives CRC progression.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},365853,1790196654,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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\nNational Cancer Center of China, China  \nREVIEWED BY  \nPing Chen,  \nTianjin Medical University Cancer Institute and Hospital, China  \nPing Zhang,  \nChina Academy of Chinese Medical Sciences, China  \n*CORRESPONDENCE  \nHe Huang  \n [Huanghe06051@163.com](Huanghe06051@163.com)[ ](Huanghe06051@163.com)Yuntong Guo  \n [docguoyuntong@163.com](docguoyuntong@163.com)  \n†These authors have contributed equally to this work  \nRECEIVED 19 March 2025  \nACCEPTED 05 May 2025  \nPUBLISHED 23 May 2025  \nCITATION  \nFan J, Liu Y, Wang J, Yao T, Bai S, Ma X, Chen H, Chen Y, Gao H, Guo Y  \nand Huang H (2025) NMB promotes the progression of colorectal cancer by regulating the NF-kB/P65 signaling pathway. Front. Immunol. 16:1596451 .  \ndoi: 10.3389/fimmu.2025.1596451  \nCOPYRIGHT  \n© 2025 Fan, Liu, Wang, Yao, Bai, Ma, Chen, Chen, Gao, Guo and Huang. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nNMB promotes the progression of colorectal cancer by regulating the NF-kB/P65 signaling pathway  \nJiaxin Fan 1,2†, Yuming Liu 1†, Jiajia Wang 3, Tian Yao 1, Shaoxiong Bai 1, Xiaole Ma 1, Hao Chen 1, Yuhao Chen 1, Huiyang Gao 1, Yuntong Guo 1* and He Huang 1*  \n1 Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China, 2 First Clinical Medical College, Shandong University, Jinan, China, 3 Department of Geriatrics, Shanxi Provincial People’s Hospital, Taiyuan, China  \nBackground: Colorectal carcinoma (CRC) ranks as the fourth most prevalent malignancy globally. Neuromedin B (NMB) and its corresponding receptor have been implicated in the pathogenesis of multiple neoplastic conditions . Nevertheless, the speciﬁc involvement of NMB in CRC progression remains poorly characterized.  \nMethods: To investigate the differential expression of NMB, data were extracted from the TCGA and GEO databases, supplemented by tissue microarrays derived from clinical specimens. Prognostic signiﬁcance was assessed through Kaplan-Meier survival analysis, ROC curve evaluation, Cox proportional hazards regression, clinical correlation studies, and nomogram construction. Experimental validation of NMB expression in CRC was performed using qRT-PCR, western blotting, immunohistochemistry, and ELISA techniques. Functional characterization of NMB's tumor-regulatory capacity was conducted through colony formation assays, MTT proliferation tests, wound healing experiments, and transwell migration/invasion assays. Mechanistic insights were obtained by identifying upstream regulatory proteins via co-immunoprecipitation and exploring potential signaling pathways through gene set enrichment analysis (GSEA) combined with western blot validation.  \nResults: Analysis of clinical data revealed that NMB exhibits markedly elevated expression levels in CRC tissues, with higher expression correlating signiﬁcantly with poor prognosis. Receiver operating characteristic curve analysis validated NMB's utility as a reliable prognostic biomarker for survival outcomes. Importantly, multivariate Cox regression analysis demonstrated NMB’s independent prognostic value in CRC patients. In vitro functional studies provided compelling evidence that NMB promotes CRC cell proliferation, migration, and invasive potential. Molecular investigations uncovered that NMB protein stability is regulated through USP21-dependent deubiquitination, leading to subsequent activation of the NF-kB signaling cascade and tumor progression. Notably, NMB expression patterns show","cbCaiePj11mZJmq7","https://ap.wps.com/l/cbCaiePj11mZJmq7","pdf",22944580,"English","# Background\n# Methods\n# Results\n# Conclusion\n# Introduction","[{\"question\":\"What was the main question of this research on colorectal cancer?\",\"answer\":\"How Neuromedin B (NMB) contributes to colorectal cancer progression and whether it can serve as a prognostic and diagnostic biomarker through its signaling regulation.\"},{\"question\":\"How was NMB expression and its prognostic value evaluated?\",\"answer\":\"NMB expression was analyzed using TCGA and GEO datasets and tissue microarrays, with prognostic significance tested using Kaplan–Meier survival analysis, ROC curves, and Cox proportional hazards regression.\"},{\"question\":\"What mechanism did the study propose for how NMB promotes tumor progression?\",\"answer\":\"NMB protein stability is regulated by USP21-dependent deubiquitination, which activates the NF-kB signaling cascade and drives CRC progression.\"}]","NMB promotes the progression of colorectal cancer by regulating the NF-kB/P65 signaling pathway | PDF",1790162625,48]