阿霉素广泛地用于晚期肝细胞癌（HCC）的化疗策略。然而，由于长期使用引起的获得性药物耐药性，临床响应令人失望。揭示潜在机制可能为耐药患者提供有希望的治疗方法。最近发现的linc-ROR（长间隔非编码RNA，重编程调节因子）已被发现在各种癌症中是一个致癌基因，并且也表明它介导药物耐药和转移。因此，我们想知道这种lincRNA是否可以介导肝癌中阿霉素化学耐药性。 在这项研究中，发现阿霉素耐药的HCC细胞中linc-ROR被上调。它的过表达加速了上皮间充质转化（EMT）程序和阿霉素耐药性。相反，它的沉默抑制了EMT，使得HCC细胞在体外和体内对阿霉素产生敏感性。进一步的研究揭示了linc-ROR与AP-2α物理相互作用，通过后翻译修饰方式介导其稳定性，随后激活Wnt/β-联蛋白途径。此外，linc-ROR的表达与人类临床样品中β-联蛋白的表达呈正相关。总之，linc-ROR通过linc-ROR/AP-2α/Wnt/β-联蛋白轴促进了肝癌的肿瘤发生和阿霉素耐药性，这可作为阿霉素耐药患者的潜在治疗靶点。©2022年作者，在Springer Nature B.V.中独家许可下发表。

Adriamycin is widely used as a chemotherapeutic strategy for advanced hepatocellular carcinoma (HCC). However, the clinical response was disappointing because of the acquired drug resistance with long-term usage. Revealing the underlying mechanism could provide promising therapeutics for the drug-resistant patients. The recently identified linc-ROR (long intergenic non-protein-coding RNA, regulator of reprogramming) has been found to be an oncogene in various cancers, and it also demonstrated to mediate drug resistance and metastasis. We thereby wonder whether this lincRNA could mediate adriamycin chemoresistance in HCC. In this study, linc-ROR was found to be upregulated in adriamycin-resistant HCC cells. And its overexpression accelerated epithelial-mesenchymal transition (EMT) program and adriamycin resistance. Conversely, its silence suppressed EMT and made HCC cells sensitize to adriamycin in vitro and in vivo. Further investigation revealed that linc-ROR physically interacted with AP-2α, mediated its stability by a post-translational modification manner, and sequentially activated Wnt/β-catenin pathway. Furthermore, linc-ROR expression was positively associated with β-catenin expression in human clinical specimens. Taken together, linc-ROR promoted tumorigenesis and adriamycin resistance in HCC via a linc-ROR/AP-2α/Wnt/β-catenin axis, which could be developed as a potential therapeutic target for the adriamycin-resistant patients.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.