[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-349402-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-349402-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","otub2-mediated-deubiquitination-upregulates-u2af2-to-promote-colorectal-cancer-evasion-of-autophagy-ferroptosis","OTUB2-mediated deubiquitination upregulates U2AF2 to promote colorectal cancer evasion of autophagy-ferroptosis","","Colorectal cancer (CRC) drives high cancer-related mortality worldwide, and ferroptosis—an iron-dependent programmed cell death—remains a therapeutic target whose evasion mechanisms are unclear. This study identifies OTUB2, a deubiquitinating enzyme, as a regulator that stabilizes U2AF2, enabling CRC cells to resist ferroptosis and autophagy. OTUB2 knockdown and overexpression were tested in CRC cell lines with functional assays and in vivo xenografts, showing that the OTUB2–U2AF2 axis disruption activates reciprocal ferroptosis and autophagy and suppresses tumor growth. Targeting this axis is proposed as a promising CRC strategy.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is the central mechanism proposed for OTUB2 in colorectal cancer?","Question",{"text":62,"@type":63},"OTUB2-mediated deubiquitination stabilizes U2AF2, allowing colorectal cancer cells to evade both ferroptosis and autophagy.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How do OTUB2 knockdown and overexpression affect ferroptosis and autophagy?",{"text":67,"@type":63},"OTUB2 knockdown increases ferroptosis and enhances autophagy, while OTUB2 overexpression reduces ferroptosis and autophagy and supports CRC cell survival and proliferation.",{"name":69,"@type":60,"acceptedAnswer":70},"What do the in vivo xenograft results show about the OTUB2–U2AF2 axis?",{"text":71,"@type":63},"Disrupting the OTUB2–U2AF2 axis impairs tumor growth by activating both ferroptosis and autophagy in xenograft models.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},349402,1790195350,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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promote colorectal cancer evasion of autophagy-ferroptosis  \nXi Chen 1,2,5, Yanxin Qi2,3,5, Qigang Nie4, Kai Zhou4 ✉ and Ao Mo 4 ✉  \n© The Author(s) 2026  \n|  |  |  |\n| --- | --- | --- |\n|  | Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a potential therapeutic target. However, the regulatory mechanisms that allow CRC cells to evade ferroptosis are not fully understood. This study focuses on OTUB2, a deubiquitinating enzyme, and its role in stabilizing U2AF2, which allows CRC cells to resist ferroptosis and autophagy. We analyzed CRC cells and clinical samples to evaluate the effects of OTUB2 on U2AF2 deubiquitination. OTUB2 knockdown and overexpression models were established in CRC cell lines (LoVo, RKO, SW480, HT115) to assess ferroptosis and autophagy activity. Various assays, including western blotting, immunoprecipitation, colony formation, and transwell migration assays, were used to evaluate cell proliferation, migration, and iron metabolism markers. In vivo xenograft models were also employed to assess tumor growth under OTUB2-U2AF2 axis disruption. OTUB2 was highly expressed in CRC tissues compared to normal controls. Knockdown of OTUB2 significantly increased ferroptosis, while enhancing autophagy. Conversely, OTUB2 overexpression reduced ferroptosis and autophagy, maintaining CRC cell survival and proliferation. In vivo studies confirmed that disrupting the OTUB2-U2AF2 axis impaired tumor growth by activating both ferroptosis and autophagy. Importantly, a reciprocal activation relationship between ferroptosis and autophagy was observed under OTUB2-U2AF2 axis deficiency. OTUB2 stabilizes U2AF2 in CRC cells, enabling them to evade ferroptosis and autophagy. Disruption of the OTUB2-U2AF2 axis activates both processes, suppressing tumor growth. Targeting this axis presents a promising |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| therapeutic strategy for CRC treatment. |  |  |\n|  | Cell Death and Disease (2026)17:607; [https://doi.org/10.1038/s41419-026-08415-8](https://doi.org/10.1038/s41419-026-08415-8) |  |\n|  |  |  |\n\nINTRODUCTION  \nColorectal cancer (CRC) originates from the epithelial cells lining the colon or rectum. It typically begins as a small, non-cancerous polyp, which may eventually develop into cancer over time. Earlystage CRC often presents with few or no symptoms; however, asthe disease progresses, patients may experience abdominal pain, rectal bleeding, and changes in bowel habits [1, 2] . Certain inherited syndromes, such as familial adenomatous polyposis (FAP) and Lynch syndrome, significantly increase the risk of developing CRC. Additionally, lifestyle factors like a high-fat and low-fiber diet, along with the consumption of red and processed meats, are associated with a higher CRC risk, whereas diets rich in fruits, vegetables, and whole grains are protective. Other risk factors include physical inactivity, obesity, smoking, and excessive alcohol consumption. Individuals with inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, are also at higher risk of developing CRC [3] .  \nOTUB2 (Otubain 2), a deubiquitinating enzyme belonging to the Ubiquitin C-terminal hydrolase (UCH) family, plays a pivotal role in regulating protein ubiquitination, particularly in maintaining protein stability through deubiquitination [4] . OTUB2 has been  \nimplicated in cell cycle regulation, influencing cell proliferation and apoptosis [5], and it plays a key role in DNA damage repair by deubiquitinating critical repair proteins to maintain genomic stability [6, 7] . Abnormal OTUB2 expression is associated with various cancers, potentially affecting tumor develop","cbCaiaIomT3JGjon","https://ap.wps.com/l/cbCaiaIomT3JGjon","pdf",6132571,14,"English","# INTRODUCTION\n## Colorectal cancer background and risk factors\n## OTUB2 and its role in ubiquitination\n## U2AF2 as a splicing factor\n## Ubiquitination–deubiquitination balance and relevance","[{\"question\":\"What is the central mechanism proposed for OTUB2 in colorectal cancer?\",\"answer\":\"OTUB2-mediated deubiquitination stabilizes U2AF2, allowing colorectal cancer cells to evade both ferroptosis and autophagy.\"},{\"question\":\"How do OTUB2 knockdown and overexpression affect ferroptosis and autophagy?\",\"answer\":\"OTUB2 knockdown increases ferroptosis and enhances autophagy, while OTUB2 overexpression reduces ferroptosis and autophagy and supports CRC cell survival and proliferation.\"},{\"question\":\"What do the in vivo xenograft results show about the OTUB2–U2AF2 axis?\",\"answer\":\"Disrupting the OTUB2–U2AF2 axis impairs tumor growth by activating both ferroptosis and autophagy in xenograft models.\"}]","OTUB2-mediated deubiquitination upregulates U2AF2 to promote colorectal cancer evasion of autophagy-ferroptosis | PDF",1790083157,35]