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Cancer stem cells contribute substantially to sorafenib resistance, and the long non-coding RNA KIF9-AS1 has previously been identified as oncogenic, though its mechanistic role in stemness and resistance is not well defined. This study investigates how N6-methyladenosine modification of KIF9-AS1 regulates cancer stemness and sorafenib resistance via SHOX2 expression.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/n6-methyladenosine-modified-long-non-coding-rna-kif9-as1-promotes-stemness-and-sorafenib-resistance-in-hepatocellular-carcinoma-by-upregulating-shox2-expression/329564/",{"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/n6-methyladenosine-modified-long-non-coding-rna-kif9-as1-promotes-stemness-and-sorafenib-resistance-in-hepatocellular-carcinoma-by-upregulating-shox2-expression/329564.png","ImageObject",300,407,{"name":92,"@type":93},"Evangeline","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main research focus regarding KIF9-AS1 and sorafenib in HCC?","Question",{"text":112,"@type":113},"The study examines how N6-methyladenosine-modified lncRNA KIF9-AS1 influences cancer stemness and promotes resistance to sorafenib in hepatocellular carcinoma, linking the effect to SHOX2 expression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were KIF9-AS1 effects on stemness and drug resistance evaluated?",{"text":117,"@type":113},"Tumor and adjacent tissue samples were collected, sphere formation was quantified, and cell viability, proliferation, apoptosis, and colony formation were assessed. Mechanistic interactions were tested using RNA immunoprecipitation and coimmunoprecipitation, and in vivo tumorigenic effects were validated in a mouse model.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular mechanism connects N6-methyladenosine modification of KIF9-AS1 to SHOX2?",{"text":121,"@type":113},"Mechanistically, N6-methyladenosine modification mediated by METTL3/IGF2BP1 stabilizes and increases KIF9-AS1, while KIF9-AS1 enhances SHOX2 stability and expression by promoting USP1-induced deubiquitination.","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},329564,1790843724,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"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,"preview_page_count":4},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","| W | J | G | World Journal of\u003Cbr>Gastroenterology |\n| --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2024 December 28; 30(48): 5174-5190  \nDOI: 10.3748/wjg.v30.i48.5174 ISSN 1007-9327 (print) ISSN 2219-2840 (online)  \nORIGINAL ARTICLE  \nBasic Study  \nN6-methyladenosine-modified long non-coding RNA KIF9-AS1 promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression  \nYong Yu, Xiang-Hong Lu, Jin-Song Mu, Jiang-Yun Meng, Jiang-Shan Sun, Hai-Xu Chen, Yang Yan, Ke Meng  \nSpecialty type: Gastroenterology and hepatology  \nProvenance and peer review:  \nUnsolicited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B, Grade C  \nNovelty: Grade A, Grade B  \nCreativity or Innovation: Grade B, Grade C  \nScientific Significance: Grade A, Grade B  \nP-Reviewer: Lin JM; Priego-Parra BA  \nReceived: June 20, 2024  \nRevised: September 26, 2024  \nAccepted: November 8, 2024  \nPublished online: December 28, 2024  \nProcessing time: 161 Days and 21.5 Hours  \nYong Yu, Jiang-Yun Meng, Jiang-Shan Sun, Ke Meng, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China  \nXiang-Hong Lu, Department of Intensive Care Medicine, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China  \nJin-Song Mu, Department of Intensive Care Medicine, The Fifth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100039, China  \nHai-Xu Chen, Institute of Geriatrics and National Clinical Research Center of Geriatrics Disease, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China  \nYang Yan, Department of General Surgery, The First Medical Center, Chinese People’s  \nLiberation Army General Hospital, Beijing 100853, China Co-first authors: Yong Yu and Xiang-Hong Lu.  \nCo-corresponding authors: Yang Yan and Ke Meng.  \nCorresponding author: Ke Meng, MD, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, [China.](China. mengke301@126.com)[ mengke301@126.com](China. mengke301@126.com)  \nAbstract  \nBACKGROUND  \nHepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC. Our previous study revealed that the long non-coding RNA (lncRNA) KIF9-AS1 is an oncogenic gene in HCC. However, the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear. Herein, we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.  \n WJG  [https://www.wjgnet.com](https://www.wjgnet.com) 5174 December 28, 2024  Volume 30  Issue 48   \nYu Y et al. KIF9-AS1 affects the progression of HCC  \nAIM  \nTo describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.  \nMETHODS  \nTumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients. Sphere formation was quantified via a tumor sphere assay. Cell viability, proliferation, and apoptosis were evaluated via Cell Counting Kit-8, flow cytometry, and colony formation assays, respectively. The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation. The tumorigenic role of KIF9-AS1 was validated in a mouse model.  \nRESULTS  \nCompared with that in normal controls, the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues. Knockdown of KIF9-AS1 inhibited stemne","cbCaitrdu43Tfhm3","https://ap.wps.com/l/cbCaitrdu43Tfhm3","pdf",9680153,18,"English","# Abstract\n## Background\n## Aim\n## Methods\n## Results\n## Conclusion\n## Key Words","[{\"question\":\"What is the main research focus regarding KIF9-AS1 and sorafenib in HCC?\",\"answer\":\"The study examines how N6-methyladenosine-modified lncRNA KIF9-AS1 influences cancer stemness and promotes resistance to sorafenib in hepatocellular carcinoma, linking the effect to SHOX2 expression.\"},{\"question\":\"How were KIF9-AS1 effects on stemness and drug resistance evaluated?\",\"answer\":\"Tumor and adjacent tissue samples were collected, sphere formation was quantified, and cell viability, proliferation, apoptosis, and colony formation were assessed. Mechanistic interactions were tested using RNA immunoprecipitation and coimmunoprecipitation, and in vivo tumorigenic effects were validated in a mouse model.\"},{\"question\":\"What molecular mechanism connects N6-methyladenosine modification of KIF9-AS1 to SHOX2?\",\"answer\":\"Mechanistically, N6-methyladenosine modification mediated by METTL3/IGF2BP1 stabilizes and increases KIF9-AS1, while KIF9-AS1 enhances SHOX2 stability and expression by promoting USP1-induced deubiquitination.\"}]","N6-methyladenosine-modified long non-coding RNA KIF9-AS1 promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression | PDF",1789984574,45]