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This study evaluates how the circular RNA circIFNGR2 affects CRC progression and links circIFNGR2 with miR-30b and KRAS using RT-qPCR, immunohistochemistry, luciferase assays, cellular functional experiments, and a xenograft model. Results show circIFNGR2 enhances CRC proliferation and migration and induces cetuximab resistance by indirectly regulating KRAS through sponging miR-30b at the post-transcriptional level, suggesting circIFNGR2 inhibition as a potential therapeutic strategy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/circifngr2-enhances-proliferation-and-migration-of-crc-and-induces-cetuximab-resistance-by-indirectly-targeting-kras-via-sponging-to-mir-30b/378586/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/circifngr2-enhances-proliferation-and-migration-of-crc-and-induces-cetuximab-resistance-by-indirectly-targeting-kras-via-sponging-to-mir-30b/378586.png","ImageObject",300,407,{"name":92,"@type":93},"OmBimo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is cetuximab resistance a concern in colorectal cancer?","Question",{"text":112,"@type":113},"Cetuximab shows clinical efficacy in CRC, but some KRAS wild-type patients develop unexpected resistance, and the underlying mechanism is unclear. The resistance limits survival benefits and overall treatment effectiveness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the proposed role of circIFNGR2 in CRC?",{"text":117,"@type":113},"circIFNGR2 is reported to enhance proliferation and migration of CRC cells. It also contributes to cetuximab resistance through indirect regulation of KRAS.",{"name":119,"@type":110,"acceptedAnswer":120},"How does circIFNGR2 induce cetuximab resistance?",{"text":121,"@type":113},"circIFNGR2 induces cetuximab resistance by sponging miR-30b, thereby indirectly targeting KRAS at the post-transcriptional level. This functional link supports circIFNGR2 as a potential therapeutic target.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},378586,1790270337,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090893581,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nCircIFNGR2 enhances proliferation and migration of CRC and induces cetuximab resistance by indirectly targeting KRAS via sponging to MiR-30b  \nQi Zhang 1,2,3,6, Yifeng Zheng 1,2,3,6, Jiajia Liu1,2,3,6, Xiaoxiao Tang 1,2,3, Yuan Wang1,2,3, Xianzheng Li4, Huibin Li4, Xiaoying Zhou1,2,3, Shiru Tang1,2,3, Yitao Tang1,2,3, Xiaoyan Wang 1,2,3 ✉, Han He5 ✉ and Tingting Li 1,2,3 ✉  \n© The Author(s) 2023  \n|  |  |  |\n| --- | --- | --- |\n|  | Currently the clinical efficacy of colorectal cancer (CRC) which is the most common malignant tumors over the world has not reached an ideal level. Cetuximab, the monoclonal antibody targeting the extracellular domain of EGFR, has shown its great efficacyin the promotion of apoptosis and the inhibition of tumor cells-like characteristics in numerous cancers. However certain KRAS wildtype CRC patients unexpectedly show cetuximab resistance and the specific mechanism remains unclear. Circular RNAs (circRNAs) as the promising novel type of biomarkers in the cancer diagnosis and therapy, have been reported to be related with the drug resistance. In this study, with wondering the mechanism of cetuximab resistance in KRAS wild-type CRC patients, we evaluate the impact of circIFNGR2 on CRC and detect the association among circIFNGR2, miR-30b and KRAS via various experiments such as RTqPCR, immunohistochemistry, luciferase assays, cell functional experiments and xenograft model. We conclude that circIFNGR2 induces cetuximab resistance in colorectal cancer cells by indirectly regulating target gene KRAS by sponging miR-30b at the posttranscriptional level. It is thus suggested that inhibition of circIFNGR2 can be a promising therapeutic strategy for malignant CRC |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| patients with cetuximab resistance. |  |  |\n|  | Cell Death and Disease (2023)14:24; [https://doi.org/10.1038/s41419-022-05536-8](https://doi.org/10.1038/s41419-022-05536-8) |  |\n|  |  |  |\n\nBACKGROUND  \nCurrently, colorectal cancer (CRC) has been one of the most common malignant tumors over the world [1] . Clinically, the metastasis to distant organs in CRC progression occurs in nearly half of the CRC patients and the metastasis in CRC always seriously threatens human health, leading to unfavorable prognosis and high mortality [2–4] . Thus, there is an urgent need for more effective diagnosis and treatment strategies, in which precision medicine plays a paramount role. Analysis of the mechanism of occurrence, development, invasion, metastasis and recurrence in CRC at the molecular level may not only contributes to the exploration of novel molecular targets but also the new therapies with high efficacy.  \nCetuximab exhibits promising efficacy in anti-CRC therapy, it has been applied as the first-line treatment of colon cancer, especially the metastatic CRC [5, 6]. Despite the great clinical efficacy of cetuximab such as the promotion of progression-free survival (PFS) and overall survival (OS), the improvement in the quality of life of patients and the low side effects, the benefits of cetuximab in CRC has been limited due to the chemotherapy resistance [7–9]. KRAS is the majoroncogenic driver and leads to acquired therapy resistance in CRC [10–12]. Crystal study showed mutant KRAS and about 40% of wild-  \ntype KRAS in CRC patients were resistant to cetuximab [10, 12]. Thus, it is of great significance to explore the mechanism of cetuximab resistance in CRC patients, particularly at the molecular level, and to further search for molecular markers for effective cetuximab therapy. Circular RNAs (circRNAs) are a class of endogenous long RNAs, characterized by the closed continuous loop without 5’–3’ polarity orthe polyA tail [13]. Circular RNAs have once been regarded as thenoncoding RNAs, actually in the latest few years their translational mechanism and the functions of the encoded peptides h","cbCaicdCNp08q7Dj","https://ap.wps.com/l/cbCaicdCNp08q7Dj","pdf",6568551,14,"English","# Background\n## Colorectal cancer burden and need for better therapy\n## Cetuximab efficacy and KRAS-related resistance\n## Circular RNAs and circRNAs as miRNA sponges\n## Prior evidence linking circRNAs to drug resistance","[{\"question\":\"Why is cetuximab resistance a concern in colorectal cancer?\",\"answer\":\"Cetuximab shows clinical efficacy in CRC, but some KRAS wild-type patients develop unexpected resistance, and the underlying mechanism is unclear. The resistance limits survival benefits and overall treatment effectiveness.\"},{\"question\":\"What is the proposed role of circIFNGR2 in CRC?\",\"answer\":\"circIFNGR2 is reported to enhance proliferation and migration of CRC cells. It also contributes to cetuximab resistance through indirect regulation of KRAS.\"},{\"question\":\"How does circIFNGR2 induce cetuximab resistance?\",\"answer\":\"circIFNGR2 induces cetuximab resistance by sponging miR-30b, thereby indirectly targeting KRAS at the post-transcriptional level. This functional link supports circIFNGR2 as a potential therapeutic target.\"}]","CircIFNGR2 enhances proliferation and migration of CRC and induces cetuximab resistance by indirectly targeting KRAS via sponging to MiR-30b | PDF",1790231334,35]