{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:31:04Z","timestamp":1790692264274,"version":"4.1.0"},"reference-count":45,"publisher":"Baishideng Publishing Group Inc.","issue":"48","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"BACKGROUND<\/jats:p>\n Hepatocellular 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.<\/jats:p>\n AIM<\/jats:p>\n To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.<\/jats:p>\n METHODS<\/jats:p>\n Tumor 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.<\/jats:p>\n RESULTS<\/jats:p>\n Compared with that in normal controls, the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues. Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells. Mechanistically, N6-methyladenosine modification mediated by methyltransferase-like 3\/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1 . Additionally, KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination. Furthermore, depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.<\/jats:p>\n CONCLUSION<\/jats:p>\n The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.<\/jats:p>","DOI":"10.3748\/wjg.v30.i48.5174","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T02:25:33Z","timestamp":1732847133000},"page":"5174-5190","source":"Crossref","is-referenced-by-count":9,"title":["N6-methyladenosine-modified long non-coding RNA KIF9-AS1<\/i> promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 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